Pediatrics Arun Babu

mebooksfree.
com
Pediatrics for
Medical Graduates
mebooksfree.com
Page left intentionally blank
mebooksfree.com
Pediatrics for
Medical Graduates
Arun Babu Thirunavukkarasu
MD Pediatrics (JIPMER), DAA (CMC Vellore), MBA (HM)
Fellow in Neonatal Perinatal Medicine (Canada)
Associate Professor
Department of Pediatrics
Indira Gandhi Medical College and Research Institute (IGMC&RI)
A Government of Puducherry Institution
Puducherry, India
mebooksfree.com
ELSEVIER
RELX India Pvt. Ltd.
Registered Office: 818, Indraprakash Building, 8th Floor, 21, Barakhamba Road, New Delhi-110001
Corporate Office: 14th Floor, Building No. 10B, DLF Cyber City, Phase II, Gurgaon-122 002, Haryana, India
Pediatrics for Medical Graduates, 1e, Arun Babu Thirunavukkarasu
Copyright © 2018 by RELX India Pvt. Ltd. (formerly known as Reed Elsevier India Pvt. Ltd)
All rights reserved.
ISBN: 978-81-312-5024-2
e-Book ISBN: 978-81-312-5025-9
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).
Notice
Practitioners and researchers must always rely on their own experience and knowledge in evaluating
and using any information, methods, compounds or experiments described herein. Because of rapid
advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages
should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors
or contributors in relation to the adaptation or for any injury and/or damage to persons or property as
a matter of products liability, negligence or otherwise, or from any use or operation of any methods,
products, instructions, or ideas contained in the material herein.
Content Strategist: Sheenam Aggarwal

Content Project Manager: Ayan Dhar
Cover Designer: Milind Majgaonkar
Senior Production Executive (India and SEA): Ravinder Sharma
Printed in India by EIH Ltd, Printing Press (Manesar, Haryana)
mebooksfree.com
To my parents, teachers, my wife Dr. Sharmila,
my kids Akshaya and Akash
mebooksfree.com
mebooksfree.com
Foreword
Ever-expanding knowledge in pediatrics with advances evidence based and up-to-date. Accompanied by illustra-
in basic, clinical, community-oriented, and population- tions, online supplementary materials, and theory ques-
based research has increased the study curriculum with tions of previous years, it becomes a complete compan-
new data. Time-bound MBBS course with pediatrics as a ion for a stressed out student. Every chapter has points or
core subject becomes a difficult area for an undergraduate algorithms making it easy to understand and remember.
to assimilate and reproduce in the examinations. Chapters on fluid and electrolytes, neurology, and infec-
Dr. Arun Babu is known to me during his training as tious disease are especially designed by keeping in mind
MBBS and MD (Pediatrics) student in JIPMER and is in the must-know areas for an MBBS student. This will be
constant touch after that during his career as a teacher. He very useful book for the MBBS student especially during
has a very good academic record during his education in the last phase of preparation before the final examinations
JIPMER and had special affinity to develop different means and preparation for the entrance examinations thereafter.
of simplifying the subject with rationalizing the facts, a Overall it is a commendable effort in the part of Dr. Arun
quality of a good teacher. His interpersonal relationship Babu and his supporting team of contributors to bring out
with the team members in the department and pleasant such a concise book while retaining the core contents of
manners made him a close friend to all of us. He has writ- the subject. I congratulate the team and wish success in
ten very useful books for the aspiring candidates for MD their endeavor.
and DM courses in the form of MCQs with answers and
explanations to make it convenient for the independent Prof. Dr. Niranjan Biswal, MD
entrance examination preparation.
This Pediatrics for Medical Graduates is a good endeav- Professor & Head, Department of Pediatrics,
or in this direction to help the MBBS student to acquire Jawaharlal Institute of Postgraduate Medical Education
the knowledge in an orderly manner in a short time. It is and Research (JIPMER), Puducherry, India
vii
mebooksfree.com
mebooksfree.com
Preface
It gives me a great pleasure in bringing out this book titled and retention. Students will also get free access to online
Pediatrics for Medical Graduates. This book is specifically supplementary materials from MedEnact, which includes
designed to cover undergraduate syllabus and to help the chapterwise MCQs and previous year pediatrics theory
medical students prepare for various internal assessments questions asked in various final MBBS University exami-
and university theory exams in pediatrics. nations.
As an undergraduate medical teacher for 12 years and I would like to thank my editorial team and contributors
an examiner for 4 years, I have received numerous feed- for their commitment, hard work, and trust without which
backs from my students regarding the need for a concise this book would not have seen the light of day. I would like
textbook on pediatrics. Most of the existing books are vo- to thank Elsevier India for publishing this book. I would
luminous, making focused reading, and last minute revi- like to wholeheartedly thank Mr. Ayan Dhar, Content
sion before exams difficult. This convinced and motivated Project Manager and his team for their relentless effort in
me to come up with an exam-oriented book on pediatrics bringing out this book. My sincere thanks to team Elsevier
covering the most essential and important topics. India, Dr. Renu Rawat, Mr. Arvind Koul, and Ms. Sheenam
All topics from “must know” areas prescribed in the Aggarwal for their cooperation. I extend my heartfelt grati-
syllabus from leading medical universities of India and tude to my teacher and mentor, Dr. Niranjan Biswal for
“those asked frequently” in various previous year univer- writing the Foreword for this book. Finally, I would like to
sity theory examinations have been carefully identified thank my students for their constant support and critical
and covered in this book. The content is given in a sim- appraisal on my work. I am looking forward to hearing
ple, concise, point-wise format for easy reading and reten- your feedback and am fully committed to bringing out bet-
tion. Bulleted points, bold fonts for important keywords, ter editions in the future. I believe and hope that this book
tables, figures, flow charts, and colored clinical images will will fulfill your expectations.
enhance the reading experience and revision for students. All the best!
Recent evidence-based concepts, latest guidelines, and Arun Babu Thirunavukkarasu
management algorithms are also included. The content is Website: www.drarunbabu.in
also thoroughly peer-reviewed independently by subject Email: babuarun.t@gmail.com
experts.
This book will help you understand the basics and pro- “Books are infinite in number and time is short.
vide the exact content needed for an undergraduate. This The secret of knowledge is to take what is essential”
book has a perfect mix of conceptual and factual elements
–Swami Vivekananda
along with tables and figures to help in easy understanding
ix
mebooksfree.com
mebooksfree.com
Acknowledgments
• Special thanks to my editorial team and contributors j Vigneshraja, MBBS, Surgery Resident, JIPMER,
j Balamurugan, DNB, MRCPCH, Asst. Prof. Puducherry
of Pediatrics, SLIMS, Puducherry (Metabolic j Malini, DNB Resident in ENT, IGGGH&PI,
Disorders) Puducherry
j Barathy C, DCH, DNB, Asst. Prof. of Pediatrics, j Sabarathinam M, MBBS student, IGMC&RI,
IGMCRI, Puducherry (Infectious Diseases) Puducherry
j Dinesh Kumar N, MD, Asst. Prof. of Pediatrics, j Mathiazhagi, CRRI, IGMC&RI, Puducherry
IGMCRI, Puducherry (Cardiovascular System) j Monisha J, CRRI, IGMC&RI, Puducherry
j Nishant Mittal, Junior Resident in Pediatrics, j Padmapriya, CRRI, IGMC&RI, Puducherry
JNMC, Belagavi, Karnataka (Nutrition) j Immanuel Joshua, CRRI, IGMC&RI, Puducherry
j Podhini J, MD, Asst. Prof. of Pediatrics, MGMCRI, j Priyadarshini A, MBBS, Junior Resident,
Puducherry (Respiratory System) Dept. of Pediatrics, IGMC&RI, Puducherry
j Premkumar S, MRCPCH, DNB Resident, Southern j Nandini varman, MBBS, Junior Resident,
Railway HQ Hospital, Chennai, Tamil Nadu (Fluid Dept. of Pediatrics, IGMC&RI, Puducherry
and Electrolytes) j Zubaida Begum, MBBS, Junior Resident,
j Sharmila Arun Babu, MS, Asst. Prof. of Obs & Dept. of Pediatrics, IGMC&RI, Puducherry
Gyne, IGMCRI, Puducherry (Fetal Medicine) j Preeti Singpho, MD (PGI), Senior Resident,
j Vijayadevagaran V, MBBS, Senior Resident Dept. of Pediatrics, JIPMER, Puducherry
in Pediatrics, IGMCRI, Puducherry (Genetics, j Usha Devi, MD DM, Asst Prof of Neonatology,
Rheumatology, Nephrology) SRMC&RI, Porur, Chennai
j Suthanthira Kannan, MD PSM, Senior Resident j Anil Kumar, MD (JIPMER), Assoc. Prof. of
in Community Medicine, Government Medical Pediatrics, BMC, Bengaluru, Karnataka
College, Manjeri, Kerala (Social Pediatrics) j Dilli Kumar, MD (JIPMER), Assoc. Prof. of
j Yazhini Neelambari, MD, IFPCCM, Fellow in Pediatrics, JIPMER, Puducherry
Pediatric Critical Care, SRMC&RI, Porur, Chennai, j Yasser Soliman, NICU Transport Fellow, Sick Kids,
Tamil Nadu (Pediatric Oncology) Toronto, Canada
• My sincere thanks to my colleagues from Dept. j Thirunavukkarasu D, Govt School English
of Pediatrics, IGMC&RI, Puducherry, Dr. Dinesh Lecturer (Retd), Puducherry
Kumar N, Asst. Prof. of Pediatrics, Dr. Shanthi j Sampurnam, Principal (Retd), SSVHSS, Puducherry
Ananthakrishnan, Prof. of Pediatrics, and Dr. j Vijayan D, Cash Officer (Retd), SBI, Puducherry
Umamageswari, Senior Resident, for peer-reviewing j Sagoundala, Under Secretary (Retd),
the chapters. Govt of Puducherry
• Thanks to Dr. Vijayadevagaran, Senior Resident, j Srinivasan Babu, PWD, Puducherry
Dept. of Pediatrics, IGMC&RI, Puducherry and j Dhinesh Shankar, EC Software, Chennai,
Jayaram Saibaba, CRRI, IGMC&RI, Puducherry for Tamil Nadu
their assistance in editorial work. j Rajkumar, System Engineer, Apple, CA, USA
• Thanks to j Govindaraj, MD, Director, IGMCRI, Puducherry
j Srinivas BH, MD, Assoc. Prof., Dept. of Pathology,
JIPMER, Puducherry Write to Us
j Jude Raja Antonio, MBBS, Senior Resident, • Any observations, suggestions, and criticisms are
Dept. of Pediatrics, IGMC&RI, Puducherry welcome. Write to the author at babuarun.t@gmail.com
xi
mebooksfree.com
mebooksfree.com
Contents
Foreword�� vii
Preface��ix
Acknowledgments��xi
1. Growth and Development......................................................................................................................................1

2. Adolescence and Behavioral Disorders...............................................................................................................18
3. Fluid, Electrolytes, and Acid Base Disturbances.................................................................................................26
4. Nutrition..................................................................................................................................................................39
5. Fetal and Neonatal Medicine...............................................................................................................................55
6. Genetics...................................................................................................................................................................81
7. Metabolic Disorders...............................................................................................................................................90
8. Immunology and Allergy....................................................................................................................................103
9. Rheumatology......................................................................................................................................................117
10. Infectious Diseases.............................................................................................................................................. 126
11. Hematology......................................................................................................................................................... 158
12. Gastrointestinal System...................................................................................................................................... 176
13. Cardiovascular System........................................................................................................................................ 200
14. Respiratory System...............................................................................................................................................231
15. Nephrology.......................................................................................................................................................... 245
16. Neurology............................................................................................................................................................ 266
17. Endocrinology..................................................................................................................................................... 289
18. Pediatric Oncology.............................................................................................................................................. 303
19. Dermatology.........................................................................................................................................................321
20. Poisoning and Envenomation.......................................................................................................................... 332
21. Social Pediatrics................................................................................................................................................... 345
Index............................................................................................................................................................................... 355
Online supplementary materials:

Please visit MedEnact to access chapter wise MCQs and previous year pediatrics theory questions asked in various final
MBBS University examinations.
xiii
mebooksfree.com
mebooksfree.com
Growth and development
- Multiple pregnancies, medical illnesses,

1.1 Growth maternal infections, drugs, irradiation, stress,
post-maturity, and abnormal presentation
• Growth represents increase in the size or mass of tissues - Obstetric disorders such as pregnancy induced
• Occurs due to multiplication of cells and increase in hypertension, preedampsia, and medical disorders
intracellular content of chronic nature also retard fetal growth
• Measure of physical maturation • Post-natal period:
• Assessed by quantitatively measuring body - Neonatal hypoxia and convulsions can cause
dimensions (in centimeters and kilograms) brain damage
- Children suffering from protein energy mal-
Development
nutrition, anemia, and vitamin deficiencies
• Development represents functional maturation in a
- Persistent or recurrent diarrhea and respiratory
child
tract infections
• It denotes acquisition of a variety of skills for optimal
C. Social factors:
functioning of the individual
• Socioeconomic level:
• New skills are attributed to myelination of the
- Children from families with high
nervous system
socioeconomic status are prone to develop
• Assessed qualitatively by evaluating various functions
over-weight and obesity
- They suffer from fewer infections because of
better hygienic living conditions
1.2 Factors affecting growth • Poverty-Hunger, under-nutrition and infections
are closely associated with poverty.
A. Genetic factors: • Climate-Growth rate is higher in spring and
• Phenotype-Transmission of parental traits to lower during summer months.
offspring is genetically determined • Emotional factors-Children from broken homes
• Race-Growth potential of children from various and orphans do not grow and develop at an optimal
racial groups are different. rate.
• Sex-Boys are generally taller and heavier than girls at - Anxiety, insecurity, lack of emotional support
the time of birth. Growth spurt occurs earlier in girls and love from the family can affect the
• Biorhythm and maturation-Daughters often neurochemical regulation of the hormones.
reach menarche at a similar age as their mother D. Endocrinal factors:
• Genetic disorders-Turners syndrome, Down • Following hormones are necessary for growth and
syndrome development:
B. Environmental factors: - Growth hormone
• Prenatal period: - Thyroxine
- Maternal malnutrition, anemia, tobacco, and - Androgens
alcohol abuse lead to IUGR and small sized fetus - Insulin
1
Pediatrics for Medical Graduates
E. Nutritional factors j Somatic growth curve is “Sigmoid” shaped

a. Deficiency of proteins, calories, and micro-nutrients • Gonadal growth—
b. Chronic illness can also lead to poor nutrition Growth of gonads (testis, ovary)
j
c. Over-nutrition and obesity Dormant during entire childhood

j
F. Trauma to epiphysis can retard growth j Rapid during puberty and adolescence
G. Drugs—Androgenic hormones can accelerate growth • Lymphoid growth—
but epiphyseal fusion occurs earlier j Growth of lymphoid tissues (tonsils, thymus,
H. Infections and infestations—Reduce the velocity of lymph nodes)
growth j Pronounced during infancy and mid-childhood
I. Cultural factors—Child rearing and feeding (4–8 yrs)
are strongly influenced by cultural taboos and j Acts as an organ for immunity in children (tonsils,
superstitious beliefs. thymus, and lymph nodes)
j Involution beyond puberty
• Neural growth—
Growth of brain, its coverings and spinal cord
1.3 Laws of growth
j
j Rapid in later months of pregnancy and early

months of post-natal life.
• Growth is a continuous and orderly process j More than 60% of growth achieved by 2 years and
• Growth pattern of every individual is unique >90% by 6 years of age.
• General growth pattern in human beings is
cephalocaudal and distal to proximal
• Sequence of growth is the same but the pace of 1.4 Assessment of physical growth
development can be non-uniform
• Each fetal and infantile growth spurt is a biological
process 1.4.1 Anthropometry
• At puberty growth spurt occurs due to neurohumoral
stimulation of hypophysis by the hypothalamus. 1.4.1.1 Weight
• Various tissues of the body grow at different rates • The weight of the child in nude or minimal light
(Fig. 1.1): clothing is recorded accurately using bathroom scale
• General body growth— (Fig. 1.2A) or electronic type of weighing scale (Fig. 1.2B).
j This includes whole musculo-skeletal growth • Spring balances are less accurate.
j Rapid in fetal life, first 3–4 years of life and puberty • Electronic weighing scales have accuracy of up to 0.01 kg
• Weighing scale should have minimum limit of 100 gm.
• Weighing scale should be corrected for any zero error
before measurement.
• Child is placed in the middle of weighing pan.
Figure 1.1 Growth rates of various organ systems. Figure 1.2 (A) Bathroom dial weighing scale.
mebooksfree.com
Growth and development Chapter |1|
Figure 1.2 (B) Electronic infant weighing scale. Figure 1.3 (A) Infantometer.
• Normal Range
j Weight at birth = 3–3.5 kg.
• Birth weight of an average Indian baby is 2.8 kg
• There is a loss of 10% of body weight in the first
week of life due to elimination of extravascular fluid.
• Term newborn regains lost birth weight by 7–10 days
and pre-terms by 10–14 days
• Rate of weight gain after birth
j 10 days–3months: 25–30 g/day
j 4–6 months: 20 g/day
• Infant typically doubles birth weight by 5–6 months
and triples by 1 year.
• Birth weight quadruples by 2 years and increases
5 times by 3 years.
• Formula for calculating expected weight
j For infants of age 3–12 months, Weight = (Age in
months+9)/2
j For 1 to 6 years, Weight = (Age in years × 2) + 8
j For 7 to 12 years, Weight = [(Age in years × 7)−5]/2
or (Age × 3)
• Definition of “Weight age”—it is the age of normal
child who will have the same weight as the child
under evaluation.
• Definition of “Weight for age”—percentage of ideal
weight expected for the age
j Used to diagnose and classify mal-nutrition till
5 years
j Examples: IAP Classification and Wellcome Trust
classification
1.4.1.2 Length/Height
• Length is recorded for children under 2 years of age
and standing height is measured above 2 years of age
• Instrument used to measure
In <2 years—Infantometer (Fig. 1.3A)
j
In >2 years—Stadiometer (Fig. 1.3B)

j
• Predicted Adult height = (Height at 2 years) × 2

• Expected height between 2—12 years in cm (Weech
formula) = (Age in years × 6) + 77 Figure 1.3 (B) Stadiometer.
mebooksfree.com
• Infantometer—Methodology
j Child is placed supine on a rigid measuring table
or an infantometer.
j Head is held firmly in position against a fixed
upright head board.
j Legs are straightened, keeping feet at right angles
to legs with toes pointing upward.
j The free foot board is brought into firm contact
with the child’s heels.
j Length of the baby is measured from a scale, which
is set in the measuring table
• Measurement of length of child lying on a mattress
with cloth tapes is inaccurate and not recommended.
• Standing height Measurement—Stadiometer—
Methodology
j For the standing height, the child stands upright.
j Child should remove his/her shoes and socks
before measurement.
j Heels are slightly separated and the weight is
borne evenly on both feet. Figure 1.4 Measuring head circumference.
j Heels, buttocks and back are brought in contact
with a vertical surface such a wall or height
measuring rod or a stadiometer. • The crossed tape (overlapping) method, using firm
j Child looks directly forwards and the head is pressure to compress the hair is the preferred way to
positioned in line with Frankfurt plane (the line measure the head circumference.
joining floor of external auditory meatus to the • Brain volume doubles in 1st year of life
lower margin of orbit) and biauricular plane. • Brain volume by 1 year is 72% and 83% of adult
j The head piece is kept firmly over the vertex to brain size by 2 years and 90% by 3 years
compress the hair. The measurement of height is • Dine’s formula for head circumference = ( Length/2)
then recorded. +9.5 ± 2.5
• Normal Range • Normal Range
j Average length at birth: 50 cm j In a newborn: 33–35 cm
j Average length at 1st year: 75 cm j At 6 months: 42–43 cm
j Average length at 2nd year: 87.5 cm j 1 year: 45–46 cm
• Maximum increase in height occurs in 1st year j 2 years: 47–48 cm
followed by puberty j 5 years: 50–51 cm
• Length (first 2 years ) increases by 50% in the first • Increase in head circumference after birth
year of life j 1–3 months: 2 cm/month
• Height doubles at 4 years and triples at 12 years j 4–6 months: 1 cm/month
• Mid-parental target height j 7–12 months: 0.5 cm/month
Girl j 1–3 years: 0.2 cm/month
Mother’s height (cm) + Father’s height (cm) − 13 cm 3–5 years: 1 cm/year
Target height (cm) = j
2
Boy • Micro-cephaly: Head circumference <3rd centile or
Mother’s height (cm) + Father’s height (cm) + 13 cm <−3 SD below the mean for age and sex
Target height (cm) =
2 • Macro-cephaly: Head circumference >95th percentile
j Expected adult height (cm) = Mid-parental target for age and sex
height ± 8
1.4.1.4 Chest circumference
1.4.1.3 Head circumference
• Used to check relative brain growth by comparing
• The maximum circumference of the head from the with head circumference
occipital protuberance to the supraorbital ridges on • The chest circumference is measured
the forehead is recorded using a nonstretchable tape j Midway between inspiration and expiration
(Fig. 1.4) j Crossed tape method is used.
• Measured through Occipital protuberance and j Measured at the level of nipples (4th inter-costal
supraorbital ridge space)
4
mebooksfree.com
Figure 1.5 Shakir tape.
• Head circumference > chest circumference by 2 cm in

term baby at birth
• Head circumference > chest circumference by >2 cm
in pre-term baby at birth
• Head circumference = chest circumference in 9–12
months of age.
• Chest circumference > Head circumference in more
than 12 months
• In PEM, head circumference >chest circumference Figure 1.6 Harpenden caliper.
beyond 1 year of age.
j Measured in the midarm over triceps area on the
1.4.1.5 Mid arm circumference (MAC) left side.
j Fold of skin between thumb and index finger is
• Age independent index between 6 months to 5 years held and measured.
• MAC is relatively constant between 16.5 and 17.5 cm
between 6 months and 5 years
• Methodology 1.5 Dentition
j Measured at the midpoint between the tip of
acromion process of scapula and the olecranon
of ulna when child holds the left arm by his side. • Dental development includes mineralization,
Crossed tape method is used. eruption, and exfoliation
j Accepted area for measurement is left arm • During fetal life, mineralization begins in 2nd trimester
• MAC interpretation • Primary teeth (Milk or Deciduous tooth): The teeth
j >13.5 cm is normal in the upper jaw erupt earlier than those in the lower
j 12.5–13.5 cm is moderate PEM jaw, except for lower central incisors. The sequence of
j <12.5 is severe PEM eruption
• Methods used j Lower Central incisors (appear first)—6-7 months
j Shakir tape j Upper central incisors—8–9 months
j Bangle test j Upper Lateral incisors—9–10 months
j Quack stick j Lower lateral incisors—10–12 months
j Non-stretchable measuring tape j First molars—12–15 months
• Shakir tape (Fig. 1.5) j Canines—18–21 months
j It is used for quick monitoring in community j Second molars (appears last)—21–24 months
j Measured in the middle of arm by overlapping • Permanent teeth: These erupt in the following
technique order:
• Interpretation using Shakir’s tape: j 1st molar—6–7 years
j Green zone: >13.5 cm - Normal nutritional j Central and lateral incisors—6–8 years
status j Canine and pre-molars—9–12 years
j Yellow zone: 12.5–13.5 cm -Border line j Second molars—12 years
mal-nutrition j Third molars—18 years or later
j Red zone: <12.5 cm -Severe mal-nutrition • Huge variation in normal eruption - Not a
dependable parameter to assess growth
• Expected number of primary teeth in an infant:
1.4.1.6 Skin fold thickness (Age in months—6)
• Triceps skinfold is commonly used for measurement • Delayed eruption is diagnosed when there are no
• Harpenden skin-fold caliper is used. (Fig. 1.6) teeth erupted by approximately 13 months of age
• Methodology (mean + 3 SD).
5
mebooksfree.com
Causes of delayed and Advanced dentition • Good tool to diagnose deviation of growth from
normal
Delayed dentition Advanced dentition
• If the height or weight measurements in a large
• Familial • Precocious puberty population of normal children are arranged in
• Rickets • Hyperthyroidism ascending order, a smooth bell shaped curve is
• Idiopathic; inconti- formed
nentia pigmenti • Charts are prepared by NCHS (national center of
• Endocrine causes: health statistics) 1977 by longitudinal studies and
Hypothyroidism ICMR based on cross sectional studies
• Down syndrome • In 2000 the CDC published revised growth charts
• Difference between NCHS and CDC charts are:
j CDC charts include two new BMI for age charts
Charts for infants—NCHS primarily based on
1.6 Bone age assessment
j
formula fed infants. CDC based on both breast

and formula fed infants
• It depends on j Each charts composed of seven or eight percentile
j Number, shape and size of epiphyseal centers curves (5, 10, 25, 50, 75, 95, and 100%)
j Size, shape and density of the ends of bones Gaussian or Normal Distribution:
• Tanner and Whitehouse Method • When large population is included, the curve should
• Tanner described 8–9 stages of development be symmetrical with nearly half of the observations
of ossification centers and gave them “maturity scoring” lying above and half below the median or the
• 50% of the score was given for carpal bones, 20% for 50th percentile, called as Gaussian Distribution
radius and ulna, 30% for phalanges (Fig. 1.7)
• 20 ossification centers are generally used for • Majority of measurements fall near the middle of curve
determining the bone age • The curve tapers off on either side because extreme
• These include measurements only rarely encountered.
j Carpal bones • The term standard deviation (SD) is used to represent
j Metacarpal and patella in both sexes the degree of dispersion of observations away from
j Distal and middle phalanges in boys and distal the mean.
and proximal phalanges in girls • Number of observations that lie within
j Distal and proximal toes j One standard deviation (±1 SD) is 68.3%
• Site of choice for Assessing Bone Age in various ages j Two standard deviation (±2 SD) is 95.4%
j 3 and 9 months—radiograph of shoulder is most j Three standard deviation (±3 SD) is 99.7%
helpful
j 1 and 13 years—hands and wrists
j 12 and 14 years—Elbow and hip
• Bone development:
j Earliest ossification center—Calcaneus
j Other centers at birth—Distal end of femur, Proximal
end of tibia, Head of humerus, Talus, and Cuboid
j Lower femoral epiphysis—Appears at 36 weeks
j Upper tibial Epiphysis—Appears at 38 weeks
• For 1–6 years, number of carpal centers = Age (in
years ) +1
• Other Bone age estimation methods
j Gruelich-pyle Atlas
j Gilsanz and Ratibin (GR) Atlas
1.7 Growth charts
• Definition—Charts in which growth parameters

like weight, height, head circumference and BMI are
charted over a period of time and plotted on graph
paper (also known as “Road to Health” card) Figure 1.7 Standard deviation in Guassian distribution.
mebooksfree.com
Percentile curves
• Represent frequency distribution curves.
• For example, 75th percentile curve means, 25% of the
values lie above that curve
• Allowable normal range of variation in observations
is conventionally taken between 3rd and 97th
percentile curves or mean ±2 SD.
Z scores:
• Z score is number of SDs above or below the mean.
• Thus, if a child’s weight is at 2 SD above the mean, it
is equivalent of +2Z
• If the value lies above the mean, Z score is positive,
otherwise, it is negative.
• The formula for calculating the Z score is:
Observed value − mean value
Z score =
Standard deviation
The WHO growth charts/WHO growth standards (2006)
• Derived from longitudinal and cross-sectional data
• Based on data from Multicenter Reference Study
(MGRS) 1997–2003
• Data obtained from a sample of healthy exclusively
breast-fed infants and children aged 0–5 yr and
non-smoking mothers
• Those children received adequate nutritional intake
and medical care Figure 1.8 Growth velocity.
• Data included children from 6 countries
j Brazil, Ghana, India, Norway, Oman, and United States
• Charts are descriptive of population average and • This pre-pubertal peak occurs earlier in girls (Fig. 1.8)
distribution
• Other growth charts in India
j ICDS growth chart Disorders of growth
j IAP growth chart
j Aggarwal’s chart
1.9 Short stature
1.8 Growth velocity (height velocity)
Definition:
• Definition: Rate at which the child grows (linear • Short stature is defined as
growth/height) over a period of given time j Height/length for age below 3rd centile (OR)
• One time measurement does not indicate the rate j Height/length more than 2SD below the median
of growth height for that age and sex according to the
• Plotting a child’s height and weight on a growth chart population standard
helps to determine if he or she is within the expected • Height velocity is usually <25th centile for age
normal range for his or her age • Common pediatric problem affecting 3–5% of
• Height needs to be measured serially over a period population.
of time to calculate growth velocity Etiology
• Growth velocity = Increase in height divided by A) Physiological or normal variant short stature—
time duration Accounts for most cases
• Growth velocity is a better tool for early identification j Familial
of stunting j Constitutional
• Helps in accurate prediction of final adult height B) Pathological short stature:
• Growth velocity oscillates around 50th centile j Under-nutrition
• Growth velocity is maximum in the first year of life j Chronic systemic illness
• Velocity steadily decreases beyond one year and has a – Renal: Chronic kidney disease, Nephrotic
small peak prior to puberty syndrome
7
mebooksfree.com
– Cardiopulmonary: Congenital heart disease, j Increase in US:LS ratio—Rickets, achondroplasia,

Bronchial asthma untreated congenital hypothyroidism
– Gastrointestinal and hepatic: Mal-absorption, j Decrease in US:LS ratio—Spondyloepiphyseal
Chronic liver disease dysplasia, vertebral anomalies
– Chronic severe infections j Arm span is shorter than length by 2.5 cm at birth,
j Endocrine causes: equals height by 11 years and thereafter greater
– Growth hormone deficiency than height.
– Hypothyroidism • Assessment of height velocity:
– Cushing syndrome j Increase in height over a period of time in cm/year
– Pseudo hypo-parathyroidism j If height velocity is low, pathological cause of short
– Precocious or delayed puberty stature should be suspected
j Psychosocial dwarfism (Kaspar Hauser syndrome) • Comparison with population norms:
j Children born as small for gestational age (SGA) j The height is plotted in growth charts expressed in
j Skeletal dysplasias—E.g.,: Achondroplasia centile or SD
j Nutritional—Mal-nutrition, Rickets • Comparison with child’s own genetic potential:
j Genetic syndromes— E.g.,: Turner syndrome, j Mid parental height (MPH) gives an approximate
Down syndrome. estimate of the child’s genetically determined
Proportionate Vs Disproportionate short stature. potential.
• Proportionate dwarfism is caused by genetic risk factors j MPH for boys = Mothers height (cm)+ Father s
and systemic conditions that affect growth potential height (cm)/2 + 6.5 cm
• Conditions affecting weight bearing long bones and j MPH for girls = Mothers height (cm)+ Father s
spine causes disproportionate dwarfism height (cm)/2–6.5 cm
j This value is then plotted on the growth chart at
Dispropor- 18–20 years. (Estimated target height for the child
tionate short and the percentile that he/she is likely to follow)
Proportionate short stature stature • Sexual maturity rating (SMR):
j SMR stage should be assessed in older children.
Physiological Pathological Short limb Height spurt is seen during early-puberty among
variants causes dwarfism
girls and mid-puberty in boys.
• Constitutional Pre-natal causes • Achondroplasia
j Precocious puberty can lead to early height spurt
growth delay • Intrauterine • Osteogenesis
followed by pre-mature epiphyseal fusion resulting
• Familial short growth retarda- imperfecta
stature tion • Rickets in short stature.
• TORCH Short trunk j Delayed puberty can also present with short stature
infections dwarfism in adolescents as the height spurt is also delayed.
• Chromosomal • Pott spine Diagnosis:
anomalies • Hemi-
Post-natal causes vertebra History Etiology
• Mal-nutrition • Spondylo- Low birth weight Small for gestational age
• Chronic diseases epiphyseal
• Endocrine dysplasia Polyuria Chronic kidney injury
causes (hypo- • Mucopolysac- and Renal Tubular
thyroidism) charidosis Acidosis
• Psychosocial Diarrhoea, offensive greasy Mal-absorption
short stature stools
Neonatal hypoglycemia, GH deficiency
Approach to a Child with Short Stature (Fig. 1.9): jaundice, micro-penis
• Accurate height measurement: Headache, vomiting, visual Pituitary/hypothalamic
For children below 2 years, supine length
j problem space occupying lesions
measured using infantometer. Lethargy, constipation, Hypothyroidism
j Stadiometer is used for older children (>2 years) weight gain
who can stand. Heels, buttocks, scapula and Poor dietary intake Under nutrition
occiput should be touching vertical support and
Social history Psychosocial dwarfism
head should be in Frankfurt plane.
• Assessment of body proportion: History for timing of pu- constitutional delay of
j By measuring US—LS ratio and comparison of berty in parents growth
arm span with height. Short stature in parents Familial short stature
mebooksfree.com
Figure 1.9 Diagnostic approach to Short stature in Children.
j Intake of balanced diet with macro- and micro-

Examination finding Etiology
nutrients
Disproportionate short Skeletal dysplasia, rickets, j Zinc supplementation
stature hypothyroidism • Levothyroxine for hypothyroidism
Dysmorphism Congenital syndromes • Limb lengthening procedure for skeletal dysplasia
Pallor Chronic anemia, CRF • GH replacement therapy for GH deficiency
• Monitoring the height of child.
Hypertension CRF
• Familial and constitutional stunting—
Frontal bossing, depressed GH deficiency j Diagnosis of Exclusion
nasal bridge, crowded teeth, j Continuous monitoring till puberty
small penis, midline defects j No specific treatment required
Goiter, coarse skin Hypothyroidism
Central obesity, striae Cushing syndrome
1.10 Familial Short Stature
Investigations:
Level 1 (Essential) investigations for short stature: • Child is short statured due to their own genetic
• Complete hemogram with ESR potential as determined by the parents height
• Bone age • These children are short because their parents are
• Urine analysis including microscopy, osmolality and pH short
• Stool examination for parasites, steatorrhoea, and • These children fulfil the criteria for short stature
occult blood (i.e., height is below the 3rd centile)
• Blood–urea, creatinine, venous gas, calcium, • These children have normal height and weight
phosphate, alkaline phosphatase, fasting glucose, at birth and then show a catch down growth,
albumin, and transaminase so that the height and weight come to lie on
Level 2 the target (mid-parental) centiles by the age of
2 years.
• Serum thyroxine and TSH to rule out hypothyroidism
• Karyotype to rule out turner syndrome in girls • Growth velocity remains normal throughout
childhood and adolescence
Level 3
• The body proportion is appropriate
• Celiac serology (anti-endomysial or anti-tissue trans- • There are no other abnormal physical findings on
glutaminase antibodies) and duodenal biopsy examination
• GH stimulation test with clonidine or insulin and • Chronologic age equals bone age (Bone age is normal)
serum IGF-1 level estimation
• Puberty is achieved at appropriate age (No delay)
Treatment: • Final height is within the target range
• Management depends on the etiology • Observed growth is parallel to the expected growth
• General measures curve
j Parents should be counselled to highlight the • Strong family history of short stature is present
positive aspects in child personality and not put • Diagnosis of exclusion
undue emphasis on stature. • No specific therapy is required
9
mebooksfree.com
• Management:
1.11 Constitutional growth delay j Counselling parents
j Mercasermin is tried
• These children are born with a normal length and j Good catchup growth is seen in less stressful
weight and grow normally for the first 6–12 months environment and when nurtured with love and
of life. Their growth then shows deceleration affection
leading on to height falling below 3rd centile
for age
• By 2–3 years of age, height velocity again accelerates 1.13 Tall stature
and they continue to grow just below and parallel to
the 3rd centile with a normal height velocity Causes
• Onset of puberty and adolescent growth spurt are also • Usually a normal variant (Familial tall stature)
delayed in these children • Pathological causes of tall stature
• Bone age is lower than the chronological age and
corresponds to the height age Endocrine Syndromes
• Child is short prior to onset of delayed adolescent
growth spurt • Hyperthyroidism • Homocystinuria
• Parents are of normal height. H/O delayed puberty and • Precocious puberty • Fragile X syndrome
delayed height spurt is present in one or both parents • Exogenous obesity • Sotos syndrome
• Pituitary causes (Gigantism, • Klinefelter syndrome
with eventual normal adult height
Acromegaly)
• Normal final adult height is reached
• Growth spurt and puberty are delayed
• Delayed Bone age
• Diagnosis of exclusion
• No specific therapy is required 1.14 Failure to thrive (FTT)
• Definition: This term includes infants and young

children who fail to grow and gain weight due to
1.12 Psychosocial dwarfism caloric deficiency without any other obvious cause
• Diagnostic criteria:
• Also called as emotional deprivation dwarfism, j Weight persistently below 3rd percentile for
Kasper hauser syndrome, maternal deprivation or age or
hyperphagic short stature. j Weight less than 80% of expected weight
• Seen in children with unhappy homes where • Types
emotional needs of children are totally neglected. j Organic
• Characterised by functional hypopituitarism and low j Non-organic
IGF-1 levels • Poor nutrition is the most common cause
• Inadequate response of GH to stimulation
Figure 1.10 Diagnostic approach to Tall stature in Children.
10
mebooksfree.com
Causes of FTT • Body Mass Index is the best parameter to screen

children with obesity. It is calculated using the
Organic causes Non organic causes formula, BMI= weight in kg/(height in meters)2
• Gastroesophageal reflex • Poor nutritional intake • Diagnostic criteria for obesity
• Mal-absorption • Poverty j BMI percentiles >95th percentile
• Mental retardation • Misperceptions j Weight for height >120% of ideal
• Cerebral palsy • Lack of breastfeeding • Diagnostic criteria for overweight
• Renal tubular acidosis • Feeding diluted formula j BMI between the 85th and 95th percentiles
• Congenital heart disease • Maternal mal-nutrition j Weight for height up to 120% of ideal
• Hypothyroidism, DM • Social and emotional
• Infections deprivation Etiology
• Genetic • Maternal psychological
• Lead poisoning illness Environmental changes: Genetics:
• Sweetened beverages • Bardet–Biedl syndrome
Clinical features: • High carbohydrate • Carpenter syndrome
• Children present with poor growth beverages • Leptin or leptin recep-
• Delayed development and cognitive functioning • Fast food consumption tor gene deficiency
• Decreased physical • Prader–Willi Syndrome
• Expressionless facies
activity Endocrine:
• Poor voluntary motor activity
• Sedentary life style • Cushing syndrome
• Delayed vocalization • Altered sleep pattern • GH deficiency
Diagnosis: Drugs: • Hyperinsulinism
• Based on History, Physical examination, • Corticosteroids • Hypothyroidism
Anthropometry, growth charts and investigations • Sodium valproate • Pseudo hypoparathy-
• Hemogram—For anemia, chronic infections roidism
• Urine examination—To rule out UTI
• Stool examination—To rule out infestation,
mal-absorption Comorbidities
• Tuberculin test and X-ray chest—To rule out Cardiovascular • Neurologic
Tuberculosis • Dyslipidemia j Pseudotumor cerebri
• Liver function test • Hypertension j Migraine
• BUN, serum creatinine Endocrine • Orthopedic

• Thyroid hormone assay (T3, T4, and TSH) • Type 2 diabetes j Blount disease (tibia
• Serum calcium, phosphorous, ALP—to rule out rickets mellitus vara)

Treatment: • Metabolic j Musculoskeletal
• Treatment focussed on etiology and associated syndrome problems

co-morbid factors • Polycystic ovary j Slipped capital femoral
syndrome epiphysis
• Treatment of psychosocial cause
Gastrointestinal • Psychological
• Dietary management • Gallbladder j Behavioral complications
j Increase caloric intake 120 Kcal/kg/day
disease • Pulmonary
Supplement vitamins and minerals
• Nonalcoholic j Asthma
j
• Stimulate the child fatty liver disease j Obstructive sleep apnea

• Regular affectionate interaction with parents
• Treatment of organic diseases
• If no improvement, hospitalize the child Evaluation
• Inter-disciplinary evaluation. Clinical
Complications • Height—Distinguishes between pathological (shorter)
• Growth retardation and exogenous obesity (taller)
• Developmental retardation • Detailed history is necessary
• Learning difficulties • Snoring loudly during sleep, sometimes associated
with apnea
Examination include
1.15 Obesity • Anthropometry
j Height, weight, BP
Definitions j Waist circumference, Waist hip ratio (WHR)
• Obesity is defined as excessive accumulation of fat in j Pattern of fat distribution
body parts, especially subcutaneous tissues. j Mid parental height
11
mebooksfree.com
• General physical: • Very low calorie diet only in life saving situation
Skin: acanthosis, acne, hirsutism, rashes in skin
j (extreme obesity, severe sleep apnea or
folds cardiopulmonary manifestations —Pickwickian
j Dysmorphic, features of any syndrome syndrome)
j Features of endocrine disease (Cushing’s, • Dietary therapy
hypothyroid) j Restriction of intake of snacks in between meals
• Systemic j Intake of food with low glycemic index
j Pubertal staging, including stretched penile length j Large meals with long gaps, and missed meals to
(SPL) in boys be avoided
j Fundus examination • Exercise supported by behavioral modifications
j Orthopedic problems j Monitoring, goal setting, contracting, stimulus
j Mental development and school performance control
j Self-esteem, behavior j Social reinforcement
j Reward and punishment
Laboratory j Aversion therapy
• Bone age assessment • Drug therapy
• Fasting blood glucose j Indicated only after trying life style modifications
• Complete lipid profile like diet, exercise and behavior control
• Complete thyroid profile j Metformin (insulin sensitizer)
• Insulin levels – Decrease body fat
j Hyperinsulinemia >20 IU/mL – Decrease plasma leptin/insulin/lipids
j Markers for insulin resistance j Orlistat, FDA approved for use in children above
– Homeostasis model assessment estimated 12 years of age
insulin resistance (HOMA-IR) – Potent reversible inhibitor of gastrointestinal
– HOMA-IR = (fasting insulin level µU/mL × lipases
fasting glucose in mmol/L)/22.5 – Given with meals, decreases fat absorption by
– Significant >4.39 30% causing weight loss
• Serum cortisol – Improves lipid and glycemic profiles
• Growth hormone stimulation test • Surgery
• PCOD— j Only considered for morbid obesity after
j Raised testosterone and/or intensive life style modifications and medication
dihydroepiandrosterone sulfate (DHEAS) have failed
j Altered LH/FSH ratio j Is relatively contraindicated <18yrs of age
j Polycystic changes in the ovaries j Indications for bariatric surgery:
j Proteinuria, Fatty liver, Raised serum T3 – BMI > 50 kg/m2
j Decreased sex hormone binding globulin and – BMI > 40 kg/m2 with severe complications like
pubertal levels of FSH in 7–9 year old girls OSA
(with no increase in LH) – Not responding to other non-surgical
• Serum PTH may be raised treatments
• Sleep study may reveal obstructive, central j Contra indications:
or combined apnea – Uncontrolled psychiatric illness
Management – Unresolved eating disorder
– Prader willi syndrome
• Treatment of comorbidities j Side effects:
Pathological obesity – Pulmonary embolism
• Treatment of specific etiology – Wound infection
• Replacement therapy – Micro–macro-nutrient mal-absorption
j Thyroxine in hypothyroidism – Diarrhea, Anemia, cholecystitis
j Growth hormone in Growth hormone – Dumping syndrome
deficiency
Exogenous obesity
• Education and Motivation for the family 1.16 Microcephaly
• Long term diets and activity changes
• Small permanent changes are useful than drastic • Definition : Head circumference <3rd centile
ones or < –3 SD below the mean for age and sex
12
mebooksfree.com
Causes of Microcephaly • Development is a continuous process, starting in

utero and progressing in an orderly, predictable
Primary causes Secondary causes manner until maturity.
• Familial • Congenital infections: CMV, • The sequence of attainment of milestones is
• Cri du chat Rubella, Toxoplasmosis essentially same in all children e.g.,: All babies stand
syndrome • Maternal causes : Alcohol, before they walk, reach for objects before they can
• Edward Smoking, Phenytoin, Radiation, start transferring them.
syndrome Phenylketonuria, Diabetes • Time and manner of attainment of milestones are
• Patau syn- • Acquired microcephaly : Rett variable
drome syndrome, Angelman syndrome, • Process of development progresses in a
Seckel syndrome, Zika virus cephalocaudal direction (head control → trunk
infection Infections in infancy : control → lower limb control)
Meningitis, Encephalitis
• The controls of limbs proceed in proximo-distal
• Malnutrition fashion (Shoulder control → hand control → finger
control)
• Certain primitive reflexes have to be lost before
1.17 Macrocephaly relevant milestones are attained e.g.,: palmar grasp is
lost before voluntary grasp is attained.
• Initial disorganized mass activity is gradually
• Definition: Head circumference more than 97th replaced by more specific and voluntary activity.
centile for age or more than 2 SD above of the mean
for age, sex and gestation
• Causes of Macrocephaly:
1.20 Factors affecting development
Chronic
Thickened Subdural
• Pre-natal factors:
cranium Collection Others
Intelligence quotient of parents correlates with IQ
j
• Chronic • Chronic • Hydrocephalus of the child.

anemia subdural • Cerebral gigantism j Parental attitudes, involvement, education and
• Rickets hematoma (Sotos syndrome) desire for the child.
• Osteogenesis or subdural • Storage disorders j Genetic factors: Chromosomal abnormalities
imperfecta effusion (Tay sachs disease) (Down syndrome), Fragile X, subtelomeric
• Epiphyseal • Meningitis • Leucodystrophy deletion, single gene disorders, lissencephaly,
dysplasia (Canavan’s disease) phenyl ketonuria.
j Maternal factors: Maternal drug or alcohol abuse,
PIH, hypothyroidism, mal-nutrition, fetoplacental
insufficiency, TORCH infections, exposure to free
1.18 Development
radicals, oxidants in-utero, stress.
• Neonatal risk factors:
• Definition: It is the maturation of function with j Low birth weight—Growth retardation, premature
age and is reflected by the sequential attainment of babies, hypoxia, hypoglycemia, hyperbilirubinemia
various milestones j Neonatal seizures—Malformation of brain, IEM,
• Development depends on maturation and severe hypoxia, intracranial bleed, and infections.
myelination of brain and correlates with the • Post Neonatal factors:
formation of new synapses in brain j Nutritional factors—Calorie deficiency, iodine
• Increasingly complex skills are learnt from more basic deficiency
capability j Acquired insults to brain
j Endocrine factors—Hypothyroidism
Associated impairment—Vision or hearing problems
1.19 Rules of development
j
j Others—environmental exposure (lead, mercury,

pesticides)
• There is a specific sequence of development within each • Social factors:
developmental field. Development in one field does j Parenting
not run parallel with another field (dissociation) j Poverty
• Development is intimately related to the maturation j Lack of stimulation
of nervous system j Violence and abuse
13
mebooksfree.com
1.21 Development milestones (Figs. 1.11A–I)
Gross Motor Visual Motor Language Social adaptive

Birth • Head flat in prone • Visual fixation on • Alerts to sound • Regards face
position objects
2 months • Raises head in prone • Follows object past • Smiles on touch and • Recognizes mother
• Begins to lift chest midline voice
• Vocalizes
3 months • In Ventral suspension, • Hands open • Cooing • Social Smile
head above the plane • Hand regard
of body • Holds an object
• Neck holding
4 months • Holds head steadily • Reaches with both • Laugh aloud • Likes to look around
• Supports trunk on arms together
forearms in prone • Hands to midline
• Rolls from prone to • Bidextrous grasp
supine (4–5 month)
6 months • Sits with support • Unilateral reach • Babbles • Recognizes stranger
(tripod) • Transfers object • Monosyllables • Mirror play
• Supports head and
upper torso on hands
in prone
7 months • Rolls from supine to • Unidextrous/Palmar • Stranger anxiety
prone grasp
• Pivoting in Prone
• May crawl
• Sitting without support
9 months • Crawls well • Immature pincer • Bisyllables—“Mama,” • Plays gesture games
• Pulls to stand grasp “dada,” indiscrimi- • Explores environment
• Standing with support • Holds bottle nately (crawling and cruising)
• Starting to cruise • Throws object • Understands “no” • Waves bye bye
(overhead) • Understands gestures • Plays peek a boo
(10 months)
• Object permanence
(uncovering hidden
object)
12 months • Walking with support • Mature pincer grasp • 1-2 words other than • Imitates actions
• May walk alone • Crayon marks “mama” and “dada” • Comes when called
• Creeps well • Follows 1-step com- • Plays simple ball game
• Bear walking/crawling mand with gesture • Kisses on request
15 months • Creeps up stairs • Scribbles and builds • 4–6 words • Uses cup and spoon
• Walks alone towers of 2 blocks in • Follows 1-step com- (variable until 18
• Walks backward imitation mand without gesture months)
• Jargon speech • Indicates wet pants
18 months • Runs • Scribbles spontaneously • 15-25 words • Imitates parents in tasks
• Throws objects over- • Builds tower of 3 blocks • Knows 5 body parts (Domestic mimicry)
hand while standing • Feeds self with spoon • Plays in company of
• Goes upstairs/down- • Turns 2–3 pages at a other children
stairs holding railing time • Dry by day
14
mebooksfree.com
Gross Motor Visual Motor Language Social adaptive

2 years • Walks up, and down • Imitates stroke (up or • 50 words • Parallel play
stairs one foot at a down) with pencil • 2-word sentences • Indicates need for
time • Builds tower of 7 • Follows 2-step food/drink
• Running blocks commands
• Kicks a ball • Removes clothing • Uses pronouns
• Turns 1 page at a time inappropriately
3 years • Alternates feet going • Copies a circle • ≥250 words • Knows full name, age
up the stairs • Dresses partially • 3-word sentences and gender
• Pedals tricycle • Undresses completely • Uses plurals and past • Takes turns/Group
• Unbuttons tense play
• Handedness • All pronouns • Shares
• Tower of 9 blocks • Dry by night
4 years • Alternates feet going • Copies a square/Cross • Knows colors • Plays cooperatively
downstairs • Buttons clothing • Recites songs from • Tells “tall tales”.
• Hops and skips • Dresses completely memory • Asks Questions.
• Tells small stories
5 years • Skips alternating feet • Copies triangle • Prints first name • Plays cooperative
• Jumps over lower • Ties shoes • Plays pretend games
obstacles • Spreads jam with • Knows alphabet Asks • Likes to help in
knife what a word means household tasks
• Answers all “wh-” • Obeying rules
questions
• Tells a story
• Development delay = (developmental age/

1.22 Developmental assessment chronologic age) × 100 = < 75%
• The maximum time should be spent observing when
• Development is a complex process and it is easier to the baby is with the mother
assess development under the following domains: • Factors assessed
j Gross motor development j Social responsiveness
j Fine motor skill development j Alertness
j Personal and social development j Concentration, interest and distractability
j Vision and hearing j The vocal responses, particularly, the nature,
frequency and quality of vocalization is noted
j Fine motor skills should be assessed- interest,
alertness and rapidity of responses
Figure 1.11 (A) Supports head and upper body on Figure 1.11 (B) Supports head and upper body using
forearm at 4 months. hands at 6 months.
15
mebooksfree.com
Figure 1.11 (E) Creeping.
Figure 1.11 (C) Sitting without support.
Figure 1.11 (F) Crawling.
Figure 1.11 (D) Standing with support. Figure 1.11(G) Palmar grasp.
mebooksfree.com
• Developmental quotient = Observed age of

attainment/Average age of attainment × 100
• A DQ below 70% is taken as delay and requires
detailed evaluation.
• Major developmental disorders.
j Mental retardation
j Cerebral palsy
j Attention deficit/hyperactivity disorder
j Autism spectrum disorders
j Learning disabilities
j Communication disorders
1.23 Red flag signs in child

development
Milestone Age
No visual fixation or following by 2 months
No vocalization by 6 months
Not sitting without support by 9–10 months
Not standing alone by 16 months
Not walking alone by 18 months
Figure 1.11 (H) Bidextrous grasp.
No single words by 18 months
Lack of imaginative play at 3 years
• Loss of previously attained milestones—Neuro-

regressive/Neurodegenerative disorder
1.24 ‘Development assessment’ tests
• Developmental screening tests are designed to

identify children with developmental delays who can
be further subjected to detailed assessments and early
intervention
• Commonly used developmental screening tests are
j Gesell’s Developmental Schedule
Figure 1.11 (I) Pincer grasp.
j Bayley scale of Infant Development (BSID)
j Denver Developmental Screening Test (DDST)
j Trivandrum development test
j Assessment of reflexes j Baroda Development Screening Test
j Head circumference
j Ventral suspension
j Pull to sit should be done at the end Online supplementary materials:
• Developmental assessment is done preferably before Please visit MedEnact to access chapter wise MCQs and
systemic examination. previous year pediatrics theory questions asked in various
• Vision and hearing assessments final MBBS University examinations.
17
mebooksfree.com
I2 I
Adolescence and behavioral disorders
2.1 Adolescence 2.3 Changes during adolescence
• Adolescence is a period in life characterized by

rapid changes in body size, physiology, psychology, Boys Girls
emotional, and social functioning of an individual • Growth spurt • Growth spurt
(adolescere-to grow; to mature) • Muscles develop • Breasts develop
• Period of Adolescence ranges from 10 to 19 years • Skin becomes oily • Skin becomes oily
• Healthy development of adolescents is dependent on • Shoulders broaden • Hipswiden
several complex factors: • Voice cracks • Underarm hair
• Socioeconomic circumstances • Underarm, chest hair • Pubic hair appears
• Environment in which they live and grow • Pubic hair appears • Uterus, ovaries enlarge
• Quality of relationship with their families, • Facial hair appears • External genitals
communities and peer groups • Penis, testis enlarge enlarge
• Opportunities for education and emp loyment • Erections in boys • Menarche, ovulation
• Adolescence is characterized by • Sperm production, • Sexual desire
• Rapid but uneven physical growth and development ejacu lation • Sexual attraction
• Sexua l desire • Initiation of sexua l
• Sexua l maturity and onset of sexua l activity
• Sexua l attraction behaviors.
• Desire for exploration and experimentation
• Initiation of sexual
• Development of adult mental process and self-
behaviors
identity
• Transition from dependence to relative independence
2.2 Stages of adolescence 2.4 Emotional and social changes
• Early adolescence (10-13 years) • Preoccupied with body image

• Characterized by a 'spurt of growth' and • Wants to establish own identity
development of secondary sexual characteristics • Fantasy/ daydreaming
• Mid adolescence (14-16 years) • Rapid mood changes, emotional instability
• Development of a separate identity from parents, • Attention seeking behavior
experimentation, new relationships with peer • Curious, inquisitive
groups, and opposite sex. • Full of energy and restless
• Late adolescence (17-19 years) • Self-exploration and evaluation
• Fully developed physical characteristics similar to • Conflicts with family over control
adults. They have a distinct identity, well-formed • Peer group defines behavioral code
opinions and ideas. • Formation of new relationships
18
Adolescence and behavioral disorders Chapter |2|
Micronutrient deficiencies like iron deficiency

j
2.5 Important Health problems anemia, iodine deficiency

during adolescence j Obesity
j Eating disorders
• Reproductive health problems
• Illness j Unprotected sexual intercourse
Problems related to growth and development
j
j Teenage pregnancies
like precocious or delayed puberty and short
j High maternal mortality
stature
j High perinatal mortality, high LBW rate
j Endemic infectious diseases like TB, malaria etc
Abortion related problems
• Consequences of risk taking behavior
j
j Menstrual problems
j Unintended injuries—Automobile and sports
j Reproductive tract infections
related accidents
j Intended injuries—Violence, homicide, suicide
• Mental health and related problems
j Behavior disorders
j Sexually transmitted diseases—HIV/AIDS, Herpes,
j Stress, anxiety
UTI
j Depression and suicide
j Substance abuse—Tobacco, alcohol, drug abuse
Substance use
• Nutritional problems
j
j Violent behavior
j Undernutrition
j Eating disorders—Bulimia and anorexia nervosa
2.6 Sequence of changes in puberty
• In Females
• In Males
• First visible sign of puberty is the Thelarche. It occurs

2.7 Tanner staging/Sexual maturity between 8 and 12 years
rating (SMR) • Menses begins 2–2.5 years after thelarche
(during SMR 3–4)
• Growth spurt occurs in Tanner stage 3
Girls:
Boys:
Stage Breast Pubic hair
Testicular
1 No breast tissue Same as abdominal Stage Genital changes volume Pubic hair
hair
1 Prepubertal <4 mL Same as
2 Breast bud, Minimally pigmented, abdominal hair
enlargement of areola mainly over labia
2 Early penile 4–10 mL Fine pubic hair at
3 Further enlargement of Darker and coarser growth, scrotal the base of penis
breast bud and areola hair on mons pubis enlargement,
4 Secondary mound Adult type, less pink scrotum
formed by papilla and distribution 3 Increase in 10–15 mL Increase in
areola penile length, number of hair,
5 Adult contour with Adult feminine scrotal growth darkening
projection of papilla distribution with 4 Increase in penile 15–20 mL Spread around
alone spread to medial length and width, thigh, less than
surface of thighs pigmented scrotum adult distribution
19
mebooksfree.com
• Poor socioeconomic status

• Malnutrition
• Iron deficiency anemia
Clinical associations:
• Lead poisoning
• Parasitic infections
• Iron deficiency anemia
• Mental retardation
• Vitamin and micronutrient deficiencies
• Pseudotumor cerebri
• Trichotillomania/Trichobezoar
Management-
• Alleviating psychosocial stress
• Deworming
Figure 2.1 Orchidometer. • Treatment of Iron deficiency—iron supplementation
and limiting cow’s milk intake
Testicular
Stage Genital changes volume Pubic hair 2.9 Temper tantrums
5 Adult size >20 mL Adult male
distribution • Occurs between 18 months and 3 years
• During this age,
Child begins to develop autonomy
• First visible sign of puberty is testicular enlargement
j
Starts separating from primary caregivers

• It begins around 9–10 years
j
Children can do exactly the opposite of what was

• Testicular volume is assessed using an orchidometer
j
told (negativism)
(Fig. 2.1)
• Children become frustrated and angry when they
• Growth spurt occurs in SMR 4 or when the testis cannot express their autonomy.
volumes reach approximately 10–15 ml
• Children show their frustration, opposition, defiance
with physical aggression or resistance such as biting,
crying, kicking, pushing, throwing objects, hitting
BEHAVIORAL DISORDERS: and head banging.This kind of behavior is known as
temper tantrums.
• Reaches peak by 2–3 years of life.
• Gradually subsides by age of 3–6 years as child learns
2.8 Pica to control negativism.
Management:
• Most common behavioral problem in children less • Parents should anticipate situations where temper
than 5 years of age tantrums are likely to occur.
• Persistent craving and compulsive eating of • Plan strategies to avoid those situations or manage
nonnutritive, nonedible substances over a period of effectively.
atleast 1 month • Distracting his/her attention from immediate cause or
• Common substances include plaster, charcoal, paint, changing the environment.
chalk, and earth (Geophagia) • Time out procedure for 1–5 min followed by time in
• Other less common non-edible substances like dust, by welcoming him back into social group with hug
clay, sand, and ice (pagophagia) and affectionate words.
• The action is inappropriate to developmental level of
the child and culturally unacceptable
• More common in children with intellectual disability
and autism 2.10 Breath holding spells
Etiology
• Mental retardation • Occurrence of episodic crying leading on to apnea in
• Psychosocial stress—maternal deprivation, parent children, associated with loss of consciousness and
neglect, abuse changes in postural tone.
20
mebooksfree.com
• There are four types: Chronic tic—

j
j Simple breath holding spell – Motor or vocal tic

j Cyanotic breath holding spell – Occurs daily or intermittently
j Pallid breath holding spell – More than a year due to stress
j Complicated breath holding spell j Tourette syndrome—
Clinical presentation – Severest of the tic disorders
• Reflexive episode is usually precipitated by a – Begins in early childhood
provocative stimulus like anger, frustration or pain. – Simple tics like blinking and facial tics appear
Starts with crying and progresses to complete cessation first
of breathing (apnea) and development of cyanosis – Complex motor tics manifest later
• The crying stops at full expiration when the child – After 1–2 years, vocal tics—coprolalia, grunting
becomes apneic and cyanotic or pale and barking appear
• Child may lose consciousness and lose muscle tone – ADHD and obsessive compulsive disorders are
transiently common comorbid conditions
• Severe cases may have seizures due to cerebral anoxia. • Management
• Seizure like activity may be seen but there is no j Drugs: Haloperidol, quetiapine
“postictal” phase or incontinence j Psychotherapy
• EEG is normal in these children.
• Begins around 6–18 months
• Peaks at 2 years and resolves by 5 years of age 2.12 Tourette syndrome
• Extremely rare before 6 months of age (Gilles de la Tourette syndrome)
• Affected children are often highly pampered by
caretakers.
• Immaturity of autonomic nervous system is thought • Inherited neuropsychiatric disorder with onset in
childhood
to play a role
• Characterized by history of multiple motor tics
Differential diagnosis: with at least one vocal tic. Both types of tic may not
• Seizures present concurrently
• Cyanotic Spell • Most cases present with simple motor tics, often
• Cardiac arrhythmias (long QT syndrome) before age 7 years.
• Brainstem tumor or malformation • In many cases, multiple tics and complex vocal
• H/O provoking events, stereotyped pattern of sounds, such as barking and grunting, develop over
events and presence of color change before loss of time and peak in severity by age 10–12 years.
consciousness helps in differentiating from seizures
• Shouting obscene words (coprolalia) is characteristic,
Management: but is seen in only 10% of affected patients.
• Parents and grandparents are counseled together • It affects boys 3–4 times more often than girls.
• Determining the cause and precipitating factors • Autosomal dominant inheritance in some cases with
• Psychotherapy greater penetrance in males
• Drug therapy not recommended Tourette’s Disorder—DSM-5 Criteria
• Treatment of coexisting IDA—iron supplementation
(3 mg/kg/day) is effective A. Multiple motor and one or more vocal tics present
B. Tics have persisted for more than 1 year since its onset
C. Onset <18 years
2.11 Tics D. Tics are not attributable to any other cause. (Cocaine
abuse, Huntington disease, postviral encephalitis)
• Involuntary and purposeless movements or utterances
that is sudden, spasmodic and repetitive. Treatment
• Mostly involve muscles of eyes, mouth, face, and neck • Symptoms characteristically wax and wane over time.
• Ranges from simple blinking, facial twitching, Severe symptoms are suppressed with drugs
vocalizations (coprolalia) • First-line treatment—neuroleptics
• Male to female ratio is 2:1 j Haloperidol (0.15 mg/kg/day) and
• Types of tics pimozide(0.05–0.2 mg/kg/day)
j Transient tic— j Dopaminergic antagonists
– Mild tics • Clonidine, an α2 agonist, is effective (0.02–0.4 mg/
– Occurs several times daily kg/day). Sedation and low blood pressure are
– Lasts for 4 weeks to 12 months common side effects that require careful monitoring.
21
mebooksfree.com
• Due to the potentially severe side effects associated • Bladder strengthening exercises
with traditional neuroleptics, most clinicians • Pharmacological treatment:
recommend risperidone (0.5–2 mg once daily). j Second line treatment—success rate is 50%
Risperidone is equivalent to clonidine in reducing tics. j Therapy should be continued for 3–6 months and
• Psychotherapy then weaned in 3–4 weeks.
• Treatment of associated obsessive-compulsive j Drugs
symptoms or attention and impulsivity problems. – Oral desmopression (drug of choice)
– Oxybutynin (Age >6 years)
– Imipramine
2.13 Nocturnal enuresis – Tolterodine
• Combination of alarm and desmopressin is more
• Involuntary voiding at night effective
• Definition: Involuntary voiding in the night beyond
the age of 5 years (Primary) or loss of acquired
urinary continence after at least 3 months of dryness
2.14 Attention deficit hyperactivity
(Secondary). disorder (ADHD)
• Normal urinary bladder emptying at a wrong place and
time at least twice a month after the age of 5 years. • Definition: Neurodevelopmental disorder
• Classification of enuresis— characterized by persistent inattention, hyperactivity,
j Primary (90%) and secondary and impulsivity causing significant impairment of
j Nocturnal and diurnal (while awake) learning and social functioning
• Etiology: • Most common neurobehavioral disorder of
j Genetic childhood affecting 3%–5% of school-aged children
j Physiological factors • Three times more common in boys
j Psychological factors • Associated with other psychiatric and neuro-
j Increased bladder irritability developmental illnesess like learning disability,
j Polyuria anxiety, depression, oppositional defiant disorder,
j Organic causes—spina bifida, ectopic ureter and conduct disorder
j Giggle and stress incontinence • Risk factors:
j Micturition deferral (waiting till last minute to pass j Maternal smoking, alcohol consumption
urine) j Abnormality in dopamine transporter gene and
• Approximately 60% cases occur in boys thyroid receptor beta gene
• Family history is positive in 50 % cases j Mutations of DAT1 and DRD4 genes
• Differential diagnosis— j Lead, mercury exposure
j Urinary tract infections j Traumatic brain injury
j Diabetes insipidus j Epilepsy
Diabetes mellitus
Pathology
j
Worm infestations
• Children with ADHD have 5%–10% reduction in
j
Congenital anomalies
the brain volume
j
Treatment: • Atypical functioning in the frontal lobes, basal

• Combined approach with supportive education, ganglia, corpus callosum, and cerebellar vermis
behavior modifications, and pharmacotherapy • Functional MRI shows reduced blood flow to the
• Reassure parents. Most cases resolve spontaneously striatum
with age • Dopamine/ norepinephrine hypothesis: may be
• Secondary causes should be ruled out (UTI, DM, related to disturbances in the dopamine or nor-
diabetes insipidus) epinephrine system
• General measures: • Genetics plays a major role as evident from twin and
j Charting of dry nights and rewarding (positive family studies
re-inforcement)
j Child should void before retiring to bed Clinical manifestations:
j No fluids for 1–2 h before going to bed • These children often present with history of disruptive
j Thick clothes to cover urinary area behavior in school
j No punishment • Inattention and early distractibility
• Motivational therapy (star chart) • Impulsivity, motor restlessness and hyperactivity
• Conditioning therapy—Alarm therapy (treatment of • Difficulty with planning and organizing tasks
choice) • Emotional lability
22
mebooksfree.com
Diagnosis: – Phenothiazines—(diphenhydramine,
• Based on clinical grounds after a thorough clinical thioridazine)
interview of parents • Behaviorally oriented treatments like seating the child
j Use of behavior rating scales near teacher, engaging the child with tasks
j Direct observation of child
• Rule out other illness that might lead to similar
symptoms
• Neuropsychological evaluation using standards of IQ 2.15 STUTTERING
to rule out mental retardation
• Definition: A defect in speech characterized by
hesitation or spasmodic repetition of some syllables
• DSM 5 criteria with pauses
j Persistent inattention and/or hyperactivity—
impulsivity that interferes with functioning or
• Difficulty in pronouncing the initial consonants due
to spasm of lingual and palatal muscles
development
j Symptoms persist for at least 6 months
• Common problem in children between 2 and 5 years
of age
j Symptoms present in 2 or more settings
(e.g., home and school)
• Environmental and emotional stress or excitement
may exacerbate stuttering
j Must begin before 12-years age
j Symptoms interfere with social, academic, or Management:
occupational functioning • Reassuring the parents.
j Symptoms must not be secondary to another • Stuttering in a young child between 2 and 5 years of
disorder age usually resolves on its own.
• Speech therapy.
• Older children with late onset of stuttering—child
Management: psychologist help should be sought.
• Optimal treatment of ADHD requires combined
behavioral and medical treatment
• Behavioral therapy:
j Clear and explicit instruction to the child about 2.16 Pervasive developmental
desirable and nondesirable behavior disorders (PDD)
j Positive reinforcement of desirable behavior by
praise or small tangible rewards
j Extinction technique i.e., systematic ignoring of • PDDs are cluster of syndromes that share marked
undesirable behavior abnormalities in development of social and
j Punishments strategies like verbal reprimand, non communicative skills
verbal gestures or time out • PDD includes—autistic disorder, Rett syndrome,
Asperger syndrome, childhood disintegrative
• Medications:
j Not recommended in children below 6 years. disorders (Heller syndrome) and PDD—not specified
j Two commonly prescribed drugs are stimulant, (PDD–NOS)
methyl phenidate and non-stimulant, atomoxetine • PDD is characterized by
j Methylphenidate (first line drug) is a presynaptic j Repetitive behavior
dopaminergic agonist. Dose ranges from 5–20 mg j Impaired communication
per day in two divided doses. Side effects include j Impaired language
anorexia, headache, abdominal pain, irritability, j Cognition is normal
and growth disturbances
j Atomoxetine is a noradrenergic reuptake
inhibitor. It is started at a dose of 0.5 mg/kg/day 2.17 Autism spectrum disorders
and increased to maximum of 1.4 mg/kg/day.
Dyspepsia, nausea, reduced appetite, and weight (ASDs)
loss are the common side effects.
j Other drugs used • Disorders included under ASDs
– Antidepressants—imipramine, buproprinone j Autism
– Amphetamine derivatives j Asperger syndrome
– Magnesium pemoline j Rett syndrome
– TCAs—imipramine • ASDs are characterized by
– Alpha adrenergic agonists—clonidine j Impaired social interaction
23
mebooksfree.com
Impaired communication
j • Clinical features:
Impaired imagination
j j Clinical diagnosis can be made by 18 months
• Persistent impairment in reciprocal social of age. Common presenting symptoms include
communication, interaction and restricted, repetitive poor eye contact, inability to engage socially
patterns of behavior, or interest or emotionally with caregivers, delayed
speech, stereotypical body movements, marked
need for sameness and preference for solitary play
2.18 Autism j Older children may show bizarre preoccupation
and marked impairment in socialization
Intelligence is variable. Though commonly
• Autistic disorder (AD) is the MC among all pervasive
j
associated with mental retardation, normal

developmental disorders
intelligence or specific areas of brilliance may
• Characterized by qualitative impairment in be seen
j Verbal and nonverbal communication
j Commonly associated with learning disabilities
j Imaginative activity
and seizure disorder
j Reciprocal social interactions that develops before
j It must be differentiated from mental retardation,
the age of 3 years.
deafness, selective mutism and ADHD.
• Prevalence - 10 to 20/1000 children
• DDs
• Complex developmental disability appearing in first 3
j Seizure disorder
years of life
Tuberous sclerosis
•
j
Failure to make social contact; aloofness, lack of eye
j Fragile X syndrome
contact
• Savant syndrome—some autistic children have
• Typical child
isolated well developed skills (remote memory,
j Highly withdrawn
computation, and musical ability)
j Extreme aloofness
j Communication problems
• Investigations
j Screening tool: M—CHAT (modified checklist for
j Often lives in an isolated world of their own
autism in toddlers ) for 16–30 months age
j Poor interaction with others
j Speech and language evaluation
j Resist any change in routine
Psychological, IQ, developmental, and psychiatric
•
j
Associated features
assessments
j Learning disabilities
j EEG and MRI of brain to rule out seizure disorder
j Seizure disorder
and other organic CNS diseases
• Etiology
j Karyotyping to rule out Fragile X syndrome
j Multifactorial
j Genetic Treatment:
j Monozygotic twins • Cognitive behavior therapy
j Pre- or perinatal injury j Intensive behavioral therapy before 3 years of age.
• Risk factors j School focusing on speech and language
j Extreme prematurity development.
j Advanced maternal or paternal age j Behavioral control.
j Antenatal exposure to thalidomide, valproate, and • Psychotherapy
organophosphate
j Congenital intrauterine infections like rubella Principles on
j Closer spacing of pregnancies educational Behavioral modification
approach program
• DSM-5 diagnostic criteria • Teaching one-on- • Identifying the
j Persistent deficit in social communication and one using primary manageable problems
interaction rewards, such as • Finding reward that
j Restricted, repetitive patterns of behavior/ food as motivation works for the child
interest or activities • Teaching in small • Trying to modify the
j Symptoms must be present in early increments with behavior consistently
developmental period repetitions and repeatedly
j Clinically significant social impairment • Using total
j Symptoms not due to other causes like communication—
intellectual disability or global developmental symbols, language,
delay and visual tools
24
mebooksfree.com
• Pharmacotherapy Clinical features

j No drug can treat autism. Drugs are indicated for • Prenatal and perinatal history is apparently normal
severe cases and to treat comorbidities • Head circumference is normal at birth but is followed
– Intranasal oxytocin by postnatal deceleration of growth
– Atomoxetine • Infants have a period of normal development till 6
– Conventional antipsychotics months followed by the onset of symptoms
– Selective serotonin reuptake inhibitors • Development of stereotypic hand movements and
– Beta-blockers loss of purposeful hand movements
– Mood stabilizers • Regression of motor milestones and language (after 1
• Prognosis: factors with better prognosis are: year of age)
j Early diagnosis and intensive behavioral therapy • Regression of speech and language milestones
j Higher intelligence level • Autistic behavior is seen at 2 years (social withdrawal,
j Presence of functional speech communication dysfunction, loss of learned words
and cognitive impairment)
• Other associated features
2.19 Asperger syndrome j Sleep disturbances, night laughter, Bruxism
j Seizures, breathing irregularities, poor weight gain
j Arrhythmias, swallowing dysfunction, GERD
• Characterized by impaired social interaction along • Criteria for diagnosis:
with restricted and repetitive behavior j Period of normal psychomotor development
• Though presentation is similar to autism, there are no (0–6 months)
delays in language skills j Deceleration of head growth (3 months to 4 years)
• More common among boys. j Loss of purposeful hand movements (9 months to
• No cognitive delays are noted 2 years)
• Age appropriate self-help skills and adaptive j Classic stereotypic hand movements (1–3 years)
behaviors are present j Gait or posture dyspraxia (2–4 years)
• Children often give monologues on a topic of interest • MRI often reveals generalized atrophy of cerebral
to them regardless of other person’s involvement hemispheres
• Diagnosis confirmed by DNA analysis
• Death occurs by 3rd decade mostly due to
2.20 Rett syndrome arrhythmias
• Disorder of early brain development

• X linked dominant—always affects females Online supplementary materials:
• Caused by mutations involving methyl CpG-binding Please visit MedEnact to access chapter wise MCQs and
protein 2—MECP2 (chr Xq28), CDKL5(chr Xp22), previous year pediatrics theory questions asked in various
NetrinG1, and Fox g1 genes final MBBS University examinations.
25
mebooksfree.com
Fluid, electrolytes, and acid base disturbances
3.1.3 Osmolality
3.1 Fluid homeostasis
• Osmolality is a measure of the solute concentration,
or the number of solute particles present in solution
3.1.1 Total body water {TBW) and is independent of the size or mass of the
• TBW as a percentage of body weight varies with age. particles.
• TBW by body weight ratio is h ighest during feta l life. • Tonicity is the effective osmolality and is equal to
Water accounts for 70%-80% of a neonate's body the sum of the concentrations of all the solutes that
weight and 55%-60% body weight by 1-2 years. have the capacity to exert an osmotic force across a
• TBW continues to decrease during first year of life membrane.
reaching around 60% of body weight and remains at • The osmolality of the ECF can be determined, and it
the same level until puberty. usually equals the ICF osmolality.
• Fat tissue stores less water, so postpubertal girls • The plasma osmolality is normally 285-295 mOsm/
have lower TBW content than boys and prepubertal kg, and it is measured by the degree of freezing point
girls. depression. Serum sodium is the major determinant
of serum osmolality.
• The plasma osmolality can also
3.1.2 Fluid compartments be estimated by this formula:
{Fig. 3.1 ) Osmolality = 2 x (Na] + [glucose]/18 + (BUN]/2.8 .
• The osmolality determines the osmotic force that
• TBW consists of two major compartments: mediates the shift of water between the ICF and
• Intracellular fluid (!CF) the ECF.
• Extracellular fluid (ECF)-Includes interstitium • If the calculated osmolality is lesser than the
and intravascular space laboratory measured osmolality, then there is
• In the fetus and newborn, the ECF volume is larger another osmotically active unknown substance
than the ICF volume. By 1 year of age, the ratio of present in plasma. Examples of unmeasured
the ICF volume to the ECF vo lume approaches adult osmo les include ethanol, ethylene glycol, methanol,
levels. sucrose, sorbito l, and mannitol.
• The ICF volume is close to twice the ECF vo lume
• The ECF is further divided into the plasma water and
the interstitial fluid 3.1.4 Regulation of osmolality
• The plasma water is 5% of body weight. and volume {Fig. 3.2)
• The blood volume is approximately 8% of body
weight and the interstitial fluid is approximately 15% • Regulation of body water is controlled by its intake
of body weight. and excretion.
26
Fluid, electrolytes, and acid base disturbances Chapter |3|
Figure 3.1 (A) Changes of Body fluid ratios with age. (B) Composition of various fluid compartments in children.
Source: Merenstein & Gardners Handbook of Neonatal Intensive Care, 2011.
Figure 3.2 Regulation of osmolality and blood volume.
• Water intake is stimulated by thirst, which is regulated • ADH secretion is inhibited by hypoosmolality of
in hypothalamus. plasma
• Plasma osmolality is sensed by Osmoreceptors of • Effects of ADH includes
hypothalamus. Increased effective osmolality leads to j Increased permeability to water in renal collecting
prompt secretion of antidiuretic hormone (ADH) by ducts.
neurons in the posterior hypothalamus (supraoptic j Increased reabsorption of water into the
and paraventricular nuclei). ADH acts by binding to hypertonic renal medulla.
V2 receptors in the renal collecting ducts. j Passing concentrated urine.
• Stimuli for ADH secretion. • Aldosterone, secreted from adrenal cortex enhances
j Hyperosmolality of plasma tubular reabsorption of sodium, thereby regulating
j Fall in plasma volume the ECF volume.
27
mebooksfree.com
3.1.5 Maintenance requirements Pathophysiology

• Whenever the serum sodium is low, intracellular
Holliday–Segar Method—To calculate volume of mainte- sodium cannot move freely out of the cell to correct
nance fluids required in 24 h low sodium in ECF.
Water • Instead water is freely permitted to move across cell
membrane. This leads to shift of water from ECF to
mL/ mL/ Electrolytes ICF leading to cell swelling.
Body Weight kg/day kg/h (mEq/100 mL H2O) • In water tight compartment like brain, any swelling
of neuronal cells leads to deleterious complications
First 10 kg 100 ∼4 Na+3
like cerebral edema, increased ICP which impairs
Second 10 kg 50 ∼2 Cl−2 cortical blood flow leading to neurological
Each addi- 20 ∼1 K+2 symptoms.
tional kg • Shift of water across membrane is decided by two
factors
How to calculate maintenance fluids for 24 h j Severity of hyponatremia
Rapidity of fall in serum sodium
• For 25 kg child—1000 mL for first 10 kg + 500mL for
j
next 10 kg + 5 × 20 = 1600 mL
• Cerebral edema can be prevented if hyponatremia
develops gradually, because neurons adapt to
decreased extracellular osmolality by reducing
intracellular osmolality by extrusion of main
3.2 Hyponatremia
intracellular ions(K+ and Cl−) first and later
neosynthesized solutes (idiogenic osmoles) like
• Most common electrolyte abnormality seen in glutamate, taurine, myoinositol, and glutamine from
hospitalized patients intracellular to extracellular compartments
• Hyponatremia is defined as serum sodium less than • This induces water loss minimizing brain
135 mEq/L swelling and hence fewer symptoms in chronic
• Hyponatremia exists when the ratio of water to hyponatremia.
sodium is increased
Clinical features
• Can occur due to water retention, loss of sodium or • Symptoms occur mainly due to extracellular
redistribution of sodium and water
hypoosmolality resulting in movement of water into
• Pseudo-hyponatremia: Relatively low sodium levels the cells. Severity of symptoms correlates with the
due to expansion of plasma volume in hyperglycemia
plasma sodium level.
and hyperlipidemia. Every 100 mg/dL increase in
• Neuronal cells are extremely sensitive to the changes
glucose reduces serum sodium levels by 1.6 mEq/L
in sodium levels explaining the predominant
Etiology neurological symptoms seen in hyponatremia
Pseudo- Hyperglycemia, hyperlipidemia, • Based on the duration of hyponatremia it is divided into
hyponatremia hyperproteinemia iatrogenic— j Acute—When serum sodium falls over less than
mannitol, sucrose, glycine 48 h.
Hypovolemic Extra renal losses— j Chronic—When serum sodium falls over more
hyponatremia Gastrointestinal (vomiting, diarrhea) than 48 h. Relatively less symptomatic due to
Skin (sweating or burns) formation of idiogenic osmoles.
Third space losses (sepsis, bowel • Symptoms according to serum sodium levels—
obstruction) j 125–135 mEq/L— > Nausea, vomiting, malaise
Renal loss—Diuretic excess, j 115–125 mEq/L—> Headache, vomiting, lethargy,
postobstructive diuresis, mineralo- confusion, obtundation
corticoid deficiency, cerebral salt j Less than 115 mEq/L—> Seizures, coma,
wasting, RTA—Type II proximal permanent brain damage, brainstem herniation
Euvolemic SIADH, desmopressin acetate, and death especially if hyponatremia is rapid and
hyponatremia glucocorticoid deficiency, severe.
hypothyroidism, water intoxication • SIADH—Inappropriate and continued secretion
Iatrogenic (excess hypotonic IV of ADH inspite of normal or increased plasma
fluid), psychogenic polydipsia, volume resulting in water retention and dilutional
diluted formula, child abuse hyponatremia.
Hypervolemic CCF, cirrhosis, Nephrotic syndrome, • Cerebral salt wasting—Hyponatremia and volume
hyponatremia Protein losing enteropathy, acute/ depletion occurring in the setting of polyuria and
chronic kidney failure increased loss of urinary sodium.
28
mebooksfree.com
Diagnostic Approach:
Treatment:
• Symptomatic hyponatremia or severe hyponatremia characterized by appearance of new onset confusion,
(Na <120 mEq/L) is treated with immediate bolus of altered sensorium, seizures, quadriparesis, and even
4–6 mL/kg of 3% sodium chloride. death.
• Sodium deficit is calculated using the formula— • Hyponatremia induced seizures respond poorly to
Amount of sodium to be corrected = 0.6 × weight anticonvulsants.
in kg × (135—observed Na+ level). Sodium levels • SIADH
have to be corrected gradually over a period of j The mainstay of treatment is fluid restriction to
time. Maximum acceptable limit of serum sodium about two-thirds of the normal requirement
correction is 12 mEq/L/24 h or 18 mEq/L/48 h or j Furosemide is effective in severe hyponatremia.
0.5 mEq/L/h. Asymptomatic hyponatremia should be • Cerebral salt wasting
corrected over 48–72 h. j High-dose fludrocortisones (0.2–0.4 mg/day) is
• Rapid correction should be strictly avoided in order to tried
prevent Central Pontine Myelinolysis (CPM). CPM is
29
mebooksfree.com
Pathophysiology
3.3 Hypernatremia • Increased tonicity and osmolality in ECF leads
to movement of water from ICF to ECF. This
• Serum sodium concentration more than 145 mEq/L results in shrinkage of cells referred to as “cellular
• Relatively less common than hyponatremia dehydration.”
Etiology
• This leads to disturbance of consciousness and in
extreme situations tearing of blood vessels and
• Hypernatremia is caused by relative deficit of water intracranial bleed.
in relation to body’s sodium stores which can result • Neurons have inherent capacity to prevent cell
from the following shrinkage by producing osmotically active substances
called “idiogenic osmoles.”
Excessive Water and so-
• This protective mechanism may take few hours to
sodium Water deficit dium deficits
evolve as well as to resolve.
• Excessive • Diabetes • GI losses Clinical features
bicarbonate insipidus j Diarrhoea
• Lethargy, weakness, irritability.
ingestion • Increased in- j Emesis/
• Hypertonia, clonus, coma, seizures.
• Intravenous sensible water nasogastric
hypertonic losses suction
• High pitched cry and fever in infants.
saline j Preterm • Cutaneous • In hypernatremic dehydration ECF volume is well
• Hyperaldo- infants losses preserved and signs of dehydration are usually not
steronism j Radiant j Burns
apparent until severe dehydration occurs.
warmers j Excessive
• Indirect markers are weight loss, sunken eyes, doughy
• Inadequate sweating skin, small heart size in X-ray
intake • Renal losses • Intravascular volume is preserved due to the shift of
j Child j Osmotic water from the intracellular to the extracellular space.
abuse/ diuretics • Typically infants are less symptomatic initially but
neglect j Diabetes dehydration can set in exponentially later.
j Adipsia mellitus • The pinched abdominal skin has a “doughy” feel.
(Lack of j CKD • Rarely high-pitched cry is present.
thirst) j Postobstruc- • Brain hemorrhage is the most devastating
tive diuresis consequence
30
mebooksfree.com
• Both Central Pontine Myelinolysis and extrapontine

myelinolysis can occur
• Thrombotic complications can occur in severe cases
j Stroke
j Intracranial venous thrombosis
j Peripheral venous thrombosis
Approach to hypernatremia
Treatment j 158–170 meq/L–48h

• Management is done in 4 phases. j 171–183 meq/L–72h
j Stabilisation of the child—>Airway, breathing, j 184–196 meq/L–84h
and circulation. • Hypernatremia should be corrected slowly to avoid
j Correction of shock if present CPM.
j Hypernatremic correction • The target is to reduce serum sodium concentration
j Treatment of underlying illness by <12 mEq/L every 24 h, at rate of 0.5 mEq/L/h
• Correct shock with NS 20 mL/kg irrespective of serum • The first priority is to restore the intravascular volume.
Na and repeat if needed. The time taken for correction This can be achieved with any isotonic fluid like 0.9%
based on serum sodium levels saline or RL solution.
j 145–157 meq/L–24h • Treatment of underlying cause
31
mebooksfree.com
Causes of hypokalemia
3.4 Potassium
Decreased intake Excess loss:
• Anorexia 1. Extra renal losses:
• The intracellular concentration of potassium, is nervosa a. Diarrhea
approximately 150 mEq/L • Malnutrition b. Laxative abuse
• The high intracellular concentration of potassium, the • Poor parenteral c. Sweating
principal intracellular cation, is maintained via the nutrition 2. Renal losses:
Na+, K+-ATPase. Transcellular shift With metabolic acidosis:
• The principal hormone regulating potassium • Alkalemia a. Distal RTA,
secretion is aldosterone. • Insulin Proximal RTA
• Drugs- alpha b. DKA
3.4.1 Hypokalemia adrenergic c. Ureterosigmoidostomy.
agonists,
With metabolic alkalosis:
• Serum potassium less than 3.5 mEq/L. theophylline,
barium, tolu- Normal/low BP
ene, hydroxy- a. Vomiting, nasogastric loss
chloroquine. b. Diuretics
• Refeeding c. Bartter’s syndrome
syndrome d. Gitelman’s syndrome
• Hypoka- High BP
lemic periodic a. Renin secreting tumors
paralysis b. Conn’s syndrome
• Thyrotoxic peri- c. Adrenal adenoma/
odic paralysis hyperplasia
d. Liddle’s syndrome
32
mebooksfree.com
Pathophysiology • General rule in Potassium replacement therapy:

• Vomiting is the common cause of hypokalemia j Oral replacement is always superior in the
that also produces volume depletion and metabolic absence of paralysis or arrhythmias.
alkalosis. j IV KCL should never be infused as bolus or
• Volume depletion stimulates RAAS system that leads undiluted.
to increased Na reabsorption via the ENAC in the j Hyperkalemia can follow IV replacement; hence
Cortical collecting duct followed by loss of potassium frequent estimation of serum levels is mandatory.
along with bicarbonate. j Hypocalcemia, hyperglycemia or metabolic
• Increased renal loss of K+ occurs in Bartter, Gitelman, acidosis should not be corrected before
Fanconi’s syndrome, and loop diuretic therapy. correcting potassium.
• In conditions with high leucocyte count like j In refractory hypokalemia anticipate and correct
leukemia, cells will extract potassium from plasma if hypomagnesemia or alkalosis.
left for some time leading to spurious hypokalemia. • Severe hypokalemia(<2.5 mEq/L) / arrhythmias/ECG
• Drugs like beta 2 agonists drive potassium into cells changes:
resulting in hypokalemia. j K+ correction = 3.0—measured K+ × BW ×
Clinical Features 0.04(0.04 represent K+ plasma volume 4% BW).
• Muscle weakness both skeletal and smooth muscle. j Calculated K+ is infused over 2–3 h at a rate of
• Hypotonia, muscle weakness and cramps. 0.3–0.5 mEq/L under strict cardio-respiratory
• Phantom hernia. monitoring.
• Bradycardia and arrhythmias. • Moderate hypokalemia (2.5–3.0 mEq/L):
• It also potentiates digoxin toxicity j Corrected less aggressively.
• Paralysis is a possible complication, especially when j IV maintenance fluid K+ is raised to 40 mEq/L by
K+ levels <2.5 mEq/L. adding 10 mL of KCL in 500 mL of maintenance
• Slowing gastrointestinal motility leading on to fluid.
Paralytic ileus j Serum level should be checked every 12 h and
• Impaired bladder function with Urinary retention. replacement should be titrated accordingly.
• Polyuria and polydipsia (similar to nephrogenic • Mild hypokalemia (3.0–3.5 mEq/L):
diabetes insipidus) j Oral KCl solution or dietary supplements
such as orange juice and coconut water
ECG changes
can be given.
• Prolonged PR Interval. j Standard oral KCl solution (15 mL will give
• Reduction in T wave amplitude/flattening/inversion. 20 mEq) initiated at 2 to 3 mEq/kg/day.
• ST depression.
• Appearance of U wave.
3.4.2 Hyperkalemia
• Serum potassium level more than 5.5 mEq/L.
• Potassium plays a major role in the regulation of
biological electrical activity and creation of resting
membrane potential.
• Hyperkalemia can cause life threatening arrhythmia
and is less well tolerated than hypokalemia.
• Hyperkalemia is a medical emergency.
Treatment Clinical features
• Initial management includes stabilization of airway, • Muscle weakness and cardiac arrhythmias are the
breathing and circulation. major features.
• Specific management and correction of K+ deficit • Paresthesias, fasciculations of muscles
depends on the severity of deficit and presence of • Weakness, ascending paralysis may occur
cardiac symptoms • ECG changes:
• Due to the risk of hyperkalemia, intravenous j Peaking T waves—Earliest sign
potassium should be used very cautiously. j ST segment depression
• Oral potassium is safer, albeit not as rapid in urgent j Increased PR interval.
situations. j Flattening of P wave
• The dose of intravenous potassium is 0.5–1.0 mEq/kg, j Widening of QRS complex
usually given over 1 hr. • May progress to ventricular fibrillation and asystole.
• Hypomagnesemia can cause hypokalemia and • Chronic hyperkalemia is generally better tolerated
should be corrected simultaneously. than acute hyperkalemia.
33
mebooksfree.com
Causes of hyperkalemia
• Spurious lab values • Increased K + load • Decreased Excretion
j Hemolysis j Blood transfusion j Renal failure
j Tissue ischemia during blood j IV or oral potassium intake j Mineralocorticoid deficiency:
drawing • Transcellular shift Addison’s disease, 21 α

j Thrombocytosis j Acidosis hydroxylase deficiency,
j Leucocytosis j Drugs: β-adrenergic blockers, j 3 β hydroxysteroid
• Cellular breakdown digitalis, succinylcholine, dehydrogenase deficiency.

j Tumor lysis syndrome fluoride j Renal tubular disorders:
j Rhabdomyolysis j Hyperkalemic periodic Pseudohypoaldosteronism,

j crush injury paralysis. urinary tract obstruction.
j Hemolysis. j Insulin deficiency j Drugs: ACE inhibitors,
j Malignant hyperthermia potassium sparing

diuretics, NSAIDS, heparin,
trimethoprim, calcineurin
inhibitors.
Serum Typical ECG Possible ECG

• IV Sodium bicarbonate (7.5%) 1–2mL/kg over
10 min diluted in equal volume of 5% dextrose.
potassium appearance abnormalities
Bicarbonate drives potassium into the cells and
Mild • Peaked T waves reduces its serum concentration.
(5.5.6.6 • Prolonged PR • Insulin drives potassium into the cells but must be
mEq/L) segment administered along with dextrose infusion to prevent
Moderate • Loss of P wave hypoglycemia. Dose: 0.5–1 gm/kg of glucose with
(6.5.8.0 • Prolonged QRS 0.1–0.2 units/kg of regular insulin.
mEq/L) complex • Nebulised Salbutamol is given in the usual dose as
• ST segment elevation for asthma. Can be repeated hourly.
• Ectopic beats and • Furosemide 1–2 mg/kg IV if renal function is normal
escape rhythms and perfusion is adequate.
Sever • Progressive widening • Potassium binding gel: Kayexalate (Potassium
(>8.0 of QRS complex exchange resin) 1 gm/kg/dose orally or rectally. Can
mEq/L) • Sine wave be repeated 6–12 hourly.
• Ventricular fibrillation • Hemodialysis if all these measures fail
• Asystole or potassium is rapidly raising or it is caused
• Axis deviations by renal failure.
• Bundle branch blocks • In cases of adrenal insufficiency, hydrocortisone 10
• Fascicular blocks mg/kg IV should be started.
Treatment
• Hyperkalemia should be treated as a medical emergency 3.5 Hypocalcemia
• Treatment should not be delayed for investigation or
to exclude spurious causes. • Symptomatic ionized hypocalcemia presents with
• Principles of managing hyperkalemia neurological and cardiovascular features.
j Stabilizing membrane and managing cardiotoxicity • Fractions of serum calcium
j Promoting shift of potassium from ECF to ICF j Ionized form (50%)
j Elimination of potassium from the body. j Albumin bound (40%)
• First step in management is to stop all sources of j Complexed with phosphate, citrate etc (~10%).
additional potassium (oral, intravenous) • Normal range of total serum calcium is 8.5–
• Administration of Intravenous calcium gluconate 0.5– 10.2 mg/dL (2.1–2.5 mmol/L)
1.0 ml/kg of 10% solution diluted with equal quantity • Normal range of ionized calcium is 4.8–7.2 mg/dL
of 5% dextrose and given as slow iv over 10 min under (1.1–1.8 mmol/L). It is not affected by age or albumin
cardiac monitoring. Calcium will not reduce serum concentration. However, it is affected by acid base
K+ levels but stabilizes and protects myocardium from status (increased in acidosis and decreased
toxic effects of hyperkalemia and prevents arrthymias in alkalosis)
34
mebooksfree.com
Causes • Gastrointestinal: Dysphagia, abdominal pain,

Abdominal or biliary colic
Neonatal Older children
• Respiratory: laryngospasm (hypocalcemic stridor),
• Prematurity • Vitamin D deficiency: Bronchospasm
• Respiratory distress j Nutritional rickets • Prolonged QT interval in ECG
syndrome j Anticonvulsants
Treatment
• Infant of diabetic mother j Renal rickets, ARF
• Treatment is indicated if symptomatic or if the
• Birth asphyxia j Vitamin D
ionized calcium concentration is <0.8 mmol/L.
• Maternal dependent rickets
hyperparathyroidism j Nephrotic
• 1–2 mL/kg of 10% calcium gluconate is administered
as slow IV injection (equivalent to 9–18 mg
• Hypoparathyroidism syndrome
elemental calcium/kg or 0.225–0.45 mmol/kg)
• DiGeorge syndrome • Sepsis
• Congenital • Hypomagnesemia over 3 h with ECG monitoring. Doses are repeated
hypomagnesemia • Acute pancreatitis every 6–8 h if symptoms persist. Calcium chloride
is an alternative.
• Calcium chloride 10% solution, contains 1.36 mEq/
Clinical features mL or 27 mg/mL and calcium gluconate 10%
• Most of the cases are asymptomatic. System-wise solution, and has 0.45 mEq/mL or 9 mg/mL
symptoms include • Continuous infusion maybe required in severe cases
• Nervous system: Fasciculations, muscle spasm,
Chvostek’s and Trousseau’s signs, tetany, seizures,
Paresthesia, tetany, seizures, and muscle spasm
j Chvostek’s sign is elicited by gently tapping over 3.6 Acid base disturbances
facial nerve anterior to earlobe and subsequent
twitching of the facial muscle
j Trousseau’s sign: Carpal spasm following 3.6.1 Metabolic acidosis
inflation of sphygmomanometer over upper arm • Metabolic acidosis is characterized by decrease in
above systolic BP (Fig. 3.3) serum pH that results from.
• Cardiovascular: Hypertension or rarely hypotension, j Loss of bicarbonate.
Arrhythmias, Congestive cardiac failure j Elevated H+ ions or decreased excretion of acids.
• Primary metabolic acidosis is characterized by an
arterial pH of less than 7.35 in the absence of an
elevated PaCO2.
Causes of metabolic acidosis:
• Normal anion gap
j Diarrhea
j Renal tubular acidosis
j Acetazolamide therapy
j Urinary tract diversion (uretero-sigmoidostomy,
rectourethral fistula)
• High anion gap
j Diabetic ketoacidosis, starvation ketoacidosis
j Lactic acidosis, shock, severe anemia, liver failure.
j Poisoning: Salicylate, Paraldehyde,
Methanol,Ethylene glycol
j Uremia, Inborn errors of metabolism
j Medications: Metformin, propofol.
Pathogenesis
• Decrease in serum pH stimulates both central and
peripheral chemoreceptors controlling respiration,
resulting in increased alveolar ventilation causing pCo2
to fall, thereby raising extracellular pH towards normal.
• On average pCo2 will fall 1.2 mm of Hg for every
1 mEq/L reduction in plasma HCo3 down to a
Figure 3.3 Trousseau’s sign. minimum pCo2 of 10–15 mmHg.
35
mebooksfree.com
• Expected pCO2 can be calculated by WINTER’s • Sodium bicarbonate is indicated in the following
formula pCO2 = 1.5 × HCo3 +8 + /−2. situations.
• Primary loss of HCO3 or failure to replenish j When pH is below 7.15
the bicarbonate store depleted by daily j In cases of Salicylate poisoning
production leads to normal anion gap metabolic j Inborn errors of metabolism
acidosis. • Amount of Sodium bicarbonate is calculated using
• Retention of fixed acids, which depletes the HCO3 the formula: HCO–3 deficit (mEq) = 0.5 × body
stores by releasing their protons leads to high anion weight (Kg) × (desired—actual serum HCO–3)
gap metabolic acidosis. • Half of the HCO3 deficit is replaced acutely over 2–3
Clinical features h by 7.5% sodium bicarbonate and the remaining
• Mild metabolic acidosis presents with nausea, is replaced along with maintenance IV fluid over
vomiting, headache, and abdominal pain 12–24 h.
• Severe cases present with Kussmaul’s breathing • Potassium supplementation to prevent hypokalemia
(rapid and deep respiration), tachycardia, cerebral in cases such as diabetes mellitus
vasodilatation leading to increased ICP, altered • Calcium gluconate therapy if hypocalcemia is
mentation and coma. precipitated by correction of metabolic acidosis
• Chronic cases present with Anorexia, lethargy, poor • In severe cases of metabolic and respiratory acidosis,
weight gain and listlessness. Chronic acidemia THAM (Tris-hydroxymethylaminomethane) is more
also results in osteopenia and muscle wasting as a effective buffer used at a dose (mL) = weight (kg) ×
result of release of calcium carbonate and glutamate base deficit, over 3 × 6 h because it neutralizes acid
respectively as buffers for H+. without releasing CO2.
Management
• Underlying cause should be identified and treated 3.6.2 Metabolic alkalosis
first.
• Shock should be treated with aggressive fluid therapy • Metabolic alkalosis is characterized by an increase in
extracellular pH above 7.45 due to primary increase
and adequate oxygenation.
in plasma bicarbonate.
• Vasoactive agents (dopamine, dobutamine) should
be added only after volume replacement as they can • It is caused by:
Administration of large amounts of alkali
worsen acidosis.
j
Loss of hydrogen ions

• Routine IV sodium bicarbonate for metabolic acidosis
j
Acute volume contraction with disproportionate

is not recommended.
j
losses of chloride
Approach to metabolic acidosis:
36
mebooksfree.com
• Metabolic alkalosis leads to respiratory compensation B) Chloride resistant (urinary chloride> 20 mEq/L)
by decreasing ventilation. • High blood pressure:
• PaCO2 increases by 7 mm Hg for each 10 mEq/L j Adrenal adenoma or hyperplasia
increase in serum HCO3− concentration. However, j Renovascular disorder
respiratory compensation never exceeds a PCO2 of j Renin secreting tumor
50–60 mm Hg. j Cushing syndrome
Causes of metabolic alkalosis j CAH (11 beta hydroxysteroid dehydrogenase, 17
A) Chloride response (urinary chloride < 15 mEq/L) beta hydroxylase deficiency)
• Gastric losses: • Normal blood pressure
j Vomiting j Gitelman’s syndrome
j Nasogastric drainage j Bartter’s syndrome
Hypoparathyroidism
• Renal loss: j
j Diuretics (loop and thiazide) Pathogenesis

j Chloride loosing diarrhea • Loss of hydrochloric acid by vomiting or nasogastric
• Cystic fibrosis suction results in increased production of acid by
• Villous adenoma stomach, which in turn leads to increased generation
• Post hypercapnia syndrome. of bicarbonate.
Approach:
37
mebooksfree.com
• Significant volume contraction from fluid loss Management

promotes proximal tubular reabsorption of Na+, • The primary underlying cause should be identified
HCO3 in exchange for K+ and H+ in distal nephron. and treated
• In mineralocorticoid excess, volume expansion • Treatment is indicated only in severe metabolic
decreases proximal renal tubular Na+ reabsorption alkalosis when pH is > 7.5
and increases the delivery of Na+ to distal nephron. • Most cases respond well to volume repletion. Normal
This Na+ is reabsorbed, K+ and H+ are secreted saline with added potassium chloride is the fluid of
resulting in metabolic alkalosis and persistent volume choice
expansion and hypertension. • Ammonium chloride or arginine hydrochloride is
• Severe hypokalemia causes metabolic alkalosis by indicated in severe cases resistant to volume repletion,
shifting hydrogen ions into the cells. usually seen in the setting of vomiting or nasogastric
Clinical features aspiration.
• Symptoms are due to underlying disorder and • Chloride responsive metabolic alkalosis responds to
dyselectrolemia. volume resuscitation and chloride repletion.
• Symptoms of alkalosis include hypoventilation, • Severe renal failure and metabolic alkalosis may
confusion, altered mentation and coma. require hemodialysis or continuous renal replacement
therapy with high chloride and low bicarbonate
• Chloride responsive metabolic alkalosis often have
symptoms related to volume depletion such as thirst dialysate.
and lethargy.
• Chloride unresponsive metabolic alkalosis causes
symptoms related to hypertension Online supplementary materials:
• Severe hypokalemia can lead to arrhythmias Please visit MedEnact to access chapter wise MCQs and
• Severe alkalemia increases calcium levels resulting in previous year pediatrics theory questions asked in various
numbness tingling sensation or tetany. final MBBS University examinations.
38
mebooksfree.com
Nutrition
• Mature milk
4.1 Breastfeeding • Foremilk is the milk secreted during initial part
of breastfeeding. It contains more water content
• Exdusive demand breast feeding is recommended wh ich satisfies thirst of the baby
during first 6 months of age • Hindmilk is secreted during later part of
• Exclusive breastfeeding: Giving a breastfeeding baby breastfeeding. It is rich in fat and satisfies hunger
no other food or drink, including water, with the of the baby
exception of prescribed drugs.
• BFHI, a global program organized by UNICEF was 4.1.2 Advantages of breastfeeding
introduced in 1992 to promote exclusive breast
feeding, adopted in India in 1993 • Breast milk contains necessary nutri ents to sustain
• Mothers should consume additional 400-500 kcal appropriate growth and development during the first
and 25 g of protein during lactation 6 months of life in term infants
• Breastfeeding should be initiated within half an hour • Protection against common childhood infections and
after vaginal delivery and within 4 h after caesarean reduction in infant and under 5 mortality rates.
delivery • Breast milk is clean, safe and cheap with no risk of
• Storage of breast milk infection
• In Room temperature-for 6- 8 h • Imp roves bonding between mother and baby
• InRefrigerator(4 °C)-for24h • Breastfed babies are protected against di abetes, heart
• In Frozen state- for 3 months disease, allergic disorders etc
• Reduces postpartum bleeding, prevents anemia in
mother in addition to contraceptive effect
4.1.1 Types of breast milk • Protective factors in Breast milk
• Bile salt stimulated Lipase (BSSL)-P rotects
• Colostrum:
• Initial 40-50 mL of yellowish milk agai nst amoeba and giardia infection
• Rich in protein and immunoglobulin (IgA) • PABA-Protects against malaria
• Contains more Sodium, proteins, and • IgA-Surface protection to respiratory tract and
immunoglobulins when compared to breast milk GIT
• Contains less fat and lactose when compared to • Lactoferrin-Ensures absorption of iron and
breast milk makes it unavailable for micro organisms.

• Transitional Milk Bacteriostatic, inhibits Escherichia coli.
• Secreted during the transition from colostrum to • Bifidus factor and acidic pH-Colonization of
the mature milk lactobacillus

• Amount of immunoglobulin, proteins, vitamin A • Lactalbumin-Precursor of tryptophan which is a
and vitamin E decreases gradually neurotransmitter

• Amount of lactose, fats, energy, and water-soluble • Calcium: Phosphorus ratio > 2; Ensures good
vitamins increases calcium absorption
39
j Polyunsaturated fatty acids: Promotes brain • Proteins

growth, reduces dyslexia/hyperactivity. j Mature breast milk contains 1.1–0.9 g/dL of
j Binding proteins—Binds to thyroxine, Vitamin D, protein
and B12 j Proteins in breast milk provide amino acids for
j Bioactive factors—Promotes growth, growth and anti-infective factors (lactoferrin,
neurotransmitters immunoglobulins, lysozyme).
j The breast milk contains more whey protein
and less casein. This high whey to casein ratio
4.1.3 Nutritional composition enables formation of softer curds which are easier
of breast milk to digest.
• Breast milk contains Differences in composition between cow’s milk and
Macronutrients—Carbohydrates, proteins, and fats
j human milk
j Micronutrients—Vitamins and minerals
j Bioactive factors—Immunoglobulins and Human milk Cow’s milk
anti-infective factors Content (100 mL) (100 mL)
j Water Non-protein nitrogen 0.2 g 0.03 g
• All these components are present in adequate Protein 1.1 g 3.0 g
quantities to meet the requirements of a healthy term
Casein whey 40:60 80:20
infant for the first 6 months of life.
• Fats Lactose 7g 4.5 g
j Human breast milk contains 3.2–3.8 g/dL of fats. EFA 13% 2%
j Fats provide 50% of the total energy from breast Ca:P >2 <2
milk.
Energy: protein 70:1 25:1
j Fat is essential for neuronal gray matter
development and myelination. Calories 67 67
j Human milk is rich in cholesterol, essential fatty
acids and Ω−3 fatty acids (docosahexaenoic acid
and eicosapentaenoic acid)
Human milk also contains the enzyme lipase which
4.1.4 Breastfeeding—position and
j
digests fat. It is activated by bile salts in intestine

• Carbohydrates attachment (Fig. 4.1 A–B)
j Lactose is the chief carbohydrate in human breast • Mother can feed the baby in any comfortable position
milk as long as good attachment is achieved.
j Accounts for 50% of breast milk’s energy content. • General signs of good positioning.
j Other carbohydrates are oligosaccharides such as j Baby is turned towards mother
glucose, galactose, N-acetylglucosamine and sialic acid. j Whole body is supported
j These oligosaccharides attach to the intestinal j Baby’s head and body are in straight line
epithelial cell surface and prevents adhesion of j Baby’s abdomen touching mothers
microorganisms. j Mouth facing nipple and areola
Figure 4.1 (A) Good attachment; (B) poor attachment.

40
mebooksfree.com
Nutrition Chapter |4|
• It is important to assess how baby’s mouth is attached • Healthcare facility should implement “The Ten Steps
to mothers breast (attachment) to Successful Breastfeeding” to be qualified as “baby
• Signs of good attachment friendly” hospital
j Lips are everted j Health care staff working in maternal–child health
j Mouth wide open services should be trained to offer skilled support
j Chin touching breast for initiation and continuation of exclusive
j Lower areola not visible breastfeeding.
• Poor attachment leads to nipple damage, sore or j Low-cost breastmilk substitutes, feeding
fissures in nipple and pain resulting in inadequate bottles or teats should not be allowed inside
breastfeeding the facility.
• Common causes of poor attachment include nipple j Establishment of community outreach support
confusion (due to using feeding bottle), inexperience, systems for breastfeeding mothers.
and lack of skilled support • One of the objectives of the Innocenti Declaration
(1990) was that by 1995, governments should
ensure that all 10 steps to successful breastfeeding are
implemented in every healthcare facility.
4.2 The 10 steps to successful
breastfeeding
4.4 Complementary feeding
• Every facility providing maternity services and care for
newborn infants should follow these steps: • Optimal nutrition during the first 2 years of life is
j Written breastfeeding policy should be available important to lay down a strong foundation for growth
and the same should be communicated to all and development. Recently, the focus has been
healthcare professionals. shifted to first 1000 days of nutrition that includes
j All healthcare professionals should be trained to 270 days of intrauterine period and first 2 years of life
acquire skills necessary to implement this policy. (730 days).
j All mothers should be educated about advantages • Appropriate complementary feeding has been
of breastfeeding. recognized as an important measure to reduce
j Mothers should receive help to initiate mortality by upto 6%.
breastfeeding within 30 min of birth. UNICEF/WHO recommends the following strategies
j Mothers should be shown how to breastfeed for optimal growth of infant and young child feeding
and how to maintain lactation if they have to be practices:
separated from their babies.
• Early initiation of breastfeeding within 1 h
Newborn infants should not be given any food or
j
• Exclusive breastfeeding for first 6 months of life
drink other than breastmilk (Exclusive breastfeeding).
• Appropriate complementary feeding starting at
j Practice ‘rooming in’ and allow mothers and 6 months
infants to remain together—24 h a day.
j Mothers should be motivated to breastfeed on Principles of complementary feeding:
demand. • Begin at 6 months of age
j No artificial teats or pacifiers should be given to • Allergic foods like cow’s milk, eggs, fish, nuts, and
infants. soybeans should be avoided
j Breastfeeding support groups should be fostered • Feeding via cup rather than bottle should be
and mothers should be referred to these groups on encouraged
discharge. • Introduce one food at a time.
• Energy density should be greater than breast milk.
• Iron-containing foods like meat, iron-supplemented
cereals should be preferred
4.3 Baby-friendly hospital initiative • Zinc intake with foods such as dairy products, meat,
wheat and rice should be encouraged
• BFHI was launched to ensure that all maternal–child • Foods with low phytate enhance mineral absorption.
health services in healthcare facilities are made • Breast milk should be continued for atleast 12–24
breastfeeding friendly and support for breastfeeding months
becomes a vital point of their program as a standard • Daily intake of cow’s milk should not be above
for care. 500 mL/day in order to avoid iron deficiency anemia
• This program was started by UNICEF and WHO in • Any fluids other than breast milk and water should
Ankara, Turkey in the year 1991 not be given
41
mebooksfree.com
Anthropometry (Auxology)
Energy
needed I. Age dependent anthropometric indices
per day in A. Weight for age
Age addition to j Simplest and most widely used to diagnose
(months) breast milk Texture Frequency malnutrition
6–8 200 kcal Thick porridge 2–3 meals j Normal values depend on age
and mashed foods per day j Serial recording of weight using a growth chart is
more informative
9–11 300 kcal Finely chopped 3–4 meals
Deranged in both acute and chronic malnutrition
and mashed foods per day
j
B. Height for age

12–23 550 kcal Family foods, 3–4 meals j Deranged in chronic malnutrition and stunting
chopped or per day
mashed if
necessary Wasting Versus Stunting
• Continue breastfeeding: It is imperative that Parameter Indicates

breastfeeding is continued for at least 2 years as breast
Weight for age Underweight
milk is an important source of micronutrients, energy
and proteins. Height for age Stunting
• It can provide one third of energy needs, half of Weight for height Wasting
protein requirement and almost three fourths of
Vitamin A requirement in this age group. II. Age independent anthropometric indices
• Age independent anthropometric indices are
objective tools used to classify malnutrition and
4.5 Protein energy malnutrition
within a specific age group, these remain constant.
(PEM) A. Mid Upper arm circumference (MUAC):
j Measured between 6 and 60 months
• Clinical syndrome due to lack of appropriate amount j Measured using Shakir’s tape and Bangle test in
of proteins, energy, vitamins, and other nutrients community setting
required by the body to maintain homeostasis and j Also used to diagnose Severe acute malnutrition
normal organ function
MUAC (cm) Interpretation
4.5.1 Etiology of PEM >13.5 cm Normal
• Inadequate dietary intake 12.5–13.5 cm Mild malnutrition
Low socioeconomic status/poverty
j
11.5–12.5 cm Moderate malnutrition
Wrong food behavior due to social customs/
j
superstitions <11.5 cm Severe acute malnutrition

(SAM)
• Low birth weight
• Medical causes
j Diarrhea, pneumonia, acute febrile illness B. Body mass index (BMI) and Weight for height
j Chronic malabsorption, parasite infestation j BMI = Weight (Kg)/(Height in m)2
j Tuberculosis, asthma, heart diseases j Underweight—BMI <5th centile
• Social factors j Overweight—BMI > 85th centile
j Large families j Obesity—BMI > 95th centile
j Working mother C. Kanawati index
j Poor sanitation, drinking water, open air defecation j Mid arm circumference to head circumference ratio
j Mild malnutrition: 0.28–0.314
4.5.2 PEM—Indicators and Assessment j Moderate malnutrition: 0.25–0.279
• Diet history j Severe malnutrition: < 0.249
• Clinical features (Symptoms and Signs) D. Rao/Singh’s index
• Biochemical parameters j Weight/Height2 ratio
• Radiological features j Normal: > 0.0015
• Anthropometry j Moderate malnutrition: 0.0013–0.0015
j Gold standard in assessing nutritional status j Severe malnutrition: < 0.0013
42
mebooksfree.com
4.5.3 Classification of PEM Acute Malnutrition Chronic Malnutrition

Wellcome trust classification • ↓ Weight for age • ↓ Weight for age
• ↓ Weight for Height • ↓ Height for age
Weight for age
• Normal Height for age • Normal Weight for
(% of expected) Edema Clinical type of PEM
Height
60%–80% Present Kwashiorkor
60%–80% Absent Undernutrition
Present Marasmic Kwashiorkor
4.5.5 Theories of PEM evolution
<60%
<60% Absent Marasmus
A. Dietary hypothesis
IAP classification of malnutrition (in under—5 age j Widely accepted hypothesis
group) j Kwashiorkor is predominantly due to protein
deficiency and marasmus is due to energy
Weight for age deficiency. However most clinical cases have
Nutritional status (% of expected) combination of both.
B. Gopalan’s Dysadaptation hypothesis
Normal >80
Grade I PEM 70–80 j Gopalan’s theory of adapation states
Grade II PEM 60–70 that adaptation to malnutrition leads
Grade III PEM 50–60 to marasmic child and dysadaptation
Grade IV PEM <50 leads to Kwashiorkor.
j Adaptation includes biochemical and hormonal
changes.
If the patient has edema of nutritional origin, the letter j High levels of catabolic hormone like cortisol
K is placed in front of the grade of PEM in order to denote cause muscle and fat breakdown
kwashiorkor j Insulin and other IGFs maintain normal
protein anabolism by synthesizing albumin
4.5.4 Severe Acute Malnutrition (SAM) and beta lipoprotein from available pool of
amino acids, thereby preventing edema and
• Diagnostic criteria (any one of the following) hepatomegaly
j Weight for height < 70% of expected or < −3 Z score C. Golden’s Hypothesis of Free Radicals
j Visible wasting j Kwashiorkor results from overproduction of free
j Bilateral pitting type of edema radicals generated from infection, toxins, iron
j MUAC <11.5 cm between 6 to 60 months old etc and further complicated by derangement
WHO cut off and interpretation of malnutrition of protective mechanism to scavenge these free
WHO classification radicals
i) Acute and chronic malnutrition*
Weight Height Weight for

4.5.6 Clinical Features of PEM
for age for age height Interpretation • Hair: Flag sign, hypochromotrichia, easily pluckable
Normal Normal Normal Normal hair
Decreased Normal Decreased Acute • Skin: Xerosis, follicular hyperkeratosis, flaky paint
malnutrition dermatosis, crazy pavement dermatosis, purpura,
Decreased Decreased Normal Chronic Petechiae
malnutrition • Mucosa: Glossitis, stomatitis, cheilosis
Decreased Decreased Decreased Acute on chronic • General: Irritability, apathy, tremors
malnutrition • Face: Diffuse depigmentation, moon face, bitot
spots, conjunctival xerosis, keratomalacia, angular
ii) Moderate and Severe acute malnutrition stomatitis, cheilosis
• Tongue: Atrophic papillae
Features MAM SAM • CVS: Microcardia, cardiomegaly
Edema No Yes
• CNS: Mental confusion, psychomotor change,
sensory loss, loss of position sense, motor
Weight for height 70%–79% or <70% or
(wasting) <−2 Z score <−3 Z score weakness, loss of ankle and knee jerks and calf
MUAC (6–60 months) 11.5–13.5 cm <11.5 cm tenderness
• GIT: Hepatomegaly
43
mebooksfree.com
4.6 Spectrum of PEM
4.6.1 Kwarshiorkor (edematous

malnutrition)
• Severe condition in protein energy malnutrition
spectrum due to protein deficiency
• The essential clinical tetrad to diagnose Kwarshiorkar
j Growth retardation
j Muscle wasting with retention of subcutaneous fat
j Edema due to hypoalbuminemia
j Mental changes
• A typical child is listless, short, edematous along with
hepatomegaly, anemia and skin lesions.
• Edema
j Often present from early stages
j Secondary to hypoalbuminemia
• Extremity changes: Muscle wasting and flabby
subcutaneous tissue
• Skin changes include
j Areas of hyperpigmentation and intervened by areas
of raw denuded skin (Flaky paint dermatosis)
j Localized or generalised desquamation rarely
follows depigmentation
j Crazy pavement and mosaic pattern dermatosis.
j Reticular pigmentation and pellagra like lesions
• Hair changes Figure 4.2 Marasmus.
j Sparse and thin hair
j In dark-haired children, hair becomes streaky red
or gray (Hypochromotrichia)
• Brown fat wasting occurs first.
Areas of alopecia and easy pluckability
j
• These children are generally alert, active and have a
j Alternate bands of light and dark colour in hair good appetite in early stages of the disease.
(Flag sign)
• Irritability is a late feature.
• Psychological changes—Lethargy, irritability, apathy
• Very severe wasting is present.
and listlessness
• Weight loss, listlessness and emaciation.
• Hepatomegaly: Due to fatty liver
• The skin becomes loose as subcutaneous fat
• GIT changes disappears.
Diarrhea, vomiting and anorexia
j
• Skin becomes wrinkled and normal skin turgor is
j Malaborption, steatorrhea lost.
Clubbing
j
• Loss of fat from the sucking pads of the cheeks often
• Mineral and vitamin deficiencies occurs late.
• Increased risk of secondary infections
• Infants are frequently constipated, but a small subset
• Stupor, coma and death in severe cases may have starvation diarrhea (frequent low volume,
Clinical staging: mucoid loose stools).
• Stage 1: Pedal edema • Skeletal muscle atrophy and hypotonia.
• Stage 2: Pedal and facial edema • Abdominal distension and loops of bowel are visible
• Stage 3: Pedal, facial, chest and paraspinal edema due to hypotonia.
• Stage 4: Generalized edema with ascites • Children often have voracious appetite.
• Hypothermia and bradycardia in severe cases.
4.6.2 Marasmus (non-edematous Clinical staging:
malnutrition)
• Stage 1: Loose skin folds in axilla and groin
• Marasmas in Greek means wasting. • Stage 2: Loose skin folds in buttocks and thighs
• ‘Old man appearance’ due to wrinkling of skin and • Stage 3: Wasting of chest and abdomen
loss of subcutaneous tissue (Fig. 4.2). • Stage 4: Wasting of buccal pad of fat
44
mebooksfree.com
Comparison between Marasmus and Kwashiorkor: • The treatment involves 10 steps in 2 phases of
treatment; stabilization phase which lasts 2−7 days
Parameter Marasmus Kwashiorkor followed by rehabilitation phase which might take
Prevalence Common Rare several weeks to months (Fig. 4.3)
Weight <60% 60-80% Hypoglycaemia
Growth retardation ++ + • Blood Glucose level < 54 mg/dL.
Edema Nil ++
• Treatment:
Apathy Nil/mild ++
j Asymptomatic hypoglycemia: 50 mL of 10%
Mood Usually alert Irritable
glucose given orally or by nasogastric tube,
Appetite Good Very poor
followed by starter F75 feeds every 2 h
Hair and skin changes Nil/mild +
Fatty liver Absent /mild ++ j Symptomatic hypoglycemia: 5 mL/kg of 10%
Life threatening + ++ dextrose infusion, followed by 50 mL of 10%
S. Protein/albumin/ Low normal Very low glucose given orally or by nasogastric tube,
carriers followed by starter F75 feeds every 2 h.
Anabolism + Very low Hypothermia
Catabolism ++ + • Rectal temperature <35.5°C or axillary temperature
Response to treatment Good Poor <35°C
Biochemical indicators are low-serum protein, esp albumin fraction, • Treatment:
enzymes like esterase, amylase, lipase, cholinesterase ALP and LDH j Proper clothing, covering the head, external heat
and carrier proteins. *Serum albumin <2g/dL indicates higher risk of like overhead warmer (radiation)/ skin contact
mortality (conduction)/or heat convector (convection).
• Prevention:
4.6.3 Management of Severe j Keep the child warm and head covered, early KMC
and early feeding
Malnutrition:
Dehydration
• These children require a comprehensive and a multi- • Hydration status is difficult to assess in SAM children.
pronged in-patient treatment. • Hypovolemia and edema can coexist.
Figure 4.3 Treatment plan for ‘Severe acute malnutrition’.
45
mebooksfree.com
• Treatment • Make a gradual transition from F75 to F100

Reduced osmolarity Oral rehydration solution
j • Increase calories to 150–200 Kcals/kg/day and
along with potassium supplements for proteins to 4–6 g/kg/day
rehydration. • Add complementary feeds
j Amount depends on child’s acceptance, vomiting Sensory stimulation
and diarrhea. • Age and development appropriate play therapy
j Feeding is initiated within 2−3 h after starting for upto 30 min every day
rehydration. F75 formula is commonly used for • Physical activity as tolerated should be
this purpose. It is given on alternate hours along encouraged.
with reduced osmolarity ORS. (for e.g.,: F75 at 3,
5, and 7 h and ORS at 2, 4, 6 h) Prepare for follow up
j Care should be taken to avoid overhydration • Sensitise caretaker, complete immunization feeding and
• Prevention follow up advise
j Give reduced osmolarity ORS at 5−10 mL/kg after
each watery stool.
Condition Treatment
j Continue breastfeeding.
Hypoglycemia Asymptomatic: 50 mL of 10% dextrose
Electrolytes
(<54 mg/dL) PO/NG
• Potassium is supplemented at 3−4 mEq/kg/day for Symptomatic: 5 mL/kg of 10% dextrose IV
atleast 2 weeks.
• On day 1, give 50% MgSO4 IM once (0.3ml/kg). Hypothermia Warm clothes, KMC, warmer care, frequent
Thereafter, daily supplementation with 1 mEq/kg/d (<35.5°C) feeds, antibiotics
Severe Oxygen, IV fluids (prewarmed), warmer
• Food preparation without added salt
hypothermia care, antibiotics, temperature monitoring
Infections (<32°C)
• Multiple infections are common, majority due to Dehydration Some dehydration: ORS 5 mL/kg every
Gram negative bacteria.
30 min for 2 h, then 5–10 mL/kg/hr for
• Hypothermia and Hypoglycemia are cardinal features 5–10 h
of infection in malnourished children. Severe dehydration/ shock: RL with 5%
• Treatment D or 1/2 DNS@ 15 mL/kg over 1 h,
j Treat with parentral ampicillin 50 mg/kg/dose repeat after 1 h. consider septic shock if no
6th hourly for atleast 2 days followed by oral improvement. ORS once stable
amoxicillin 15 mg/kg 8th hourly for 5 days.
Electrolyte Potassium and magnesium supplements for
j If no improvement in 48 h, change to IV
imbalance 2 weeks
cefotaxime 100–150 mg/kg 6–8th hourly.
• Prevention Infection Ampicilin/gentamicin
j Proper cleanliness and hand hygiene. Cloxacillin for suspected staphylococcal
j Measles vaccine if indicated and missed. infection
Cefotaxime (meningitis)
Micronutrients Third generation cephalosporins (septic
• Twice the recommended daily allowance of vitamins shock)
and minerals are given. Ciprofloxacin (dysentery)
• Give Vitamin A orally on day 1, 2, and 14 Micronutrient Vitamin A, D supplements, Vitamin B
• Give folic acid at 1 mg/kg/d (5 mg on day 1) deficiency (twice RDA)
• Give zinc at 2 mg/kg/d Folic acid (5 mg on D1 then 1 mg/day),
• Give copper at 0.2–0.3 mg/kg/d zinc (2 mg/kg/day) and copper (0.3 mg/
• Give iron 3 mg/kg/d only after stabilization phase. kg/day)
Initiate feeding Iron in rehabilitation phase
• Start with small frequent feeds. Start cautious F75 diet- (75 k cal+ 0.9 g protein/100
• Continue breastfeeding feeding mL) ( rich in carbohydrate, low in
• Start with F75 diet (75 kcal and 0.9 g protein per protein/ fat)
100 mL) every 2nd hourly. Catch up F100 diet—(100 kcal + 2.9 g protein/100
• Total requirement is 130 mL/kg/day but in case of growth mL) (rich in protein/fat)
generalized edema, can be reduced to 100 mL/kg/
Sensory stimu- Emotional support
day. lation
Catch up growth Discharge and Sensitize caretaker, immunization
• Encourage higher intakes once appetite returns follow up complete, feeding and follow-up advised
• Increase volume and reduce frequency of each feed
46
mebooksfree.com
Failure of Treatment • Can be stored at home without the need of

• Inadequate weight gain (<5 g/kg/day) refrigeration and has low contamination rates.
• Poor feeding • Should be given along with continued
• Persistent infection breastfeeding.
• Specific nutritional deficiencies • At present, government of India does not approve
• Tuberculosis and HIV/AIDS RUTF.
• Psychological problems Amount of ready to use therapeutic food (RUTF):
Discharge criteria:
• Weight for height >90% and no edema Weight (kg) Amount of RUTF (g/day)
• Infection treated fully 3–4.9 105–130
• Eating at least 120–130 Kcal/kg/day and along with
adequate micronutrient supplementation 5–6.9 200–260
• Consistent weight gain of at least 5 g/kg/day for three 7–9.9 260–400
consecutive days on oral feeds 10–14.9 400–460
• Immunization up to date
• Education and counseling to caretakers
• Interactive with the surroundings and return of social 4.6.5 Nutritional recovery syndrome
smile
(Refeeding syndrome)
4.6.4 Ready to use therapeutic • Artificial refeeding in PEM patients are associated
food (RUTF) with rapid shifts in fluids and electrolytes leading to
refeeding syndrome
• RUTF are energy-dense, micronutrient-enriched
preparations that have a similar nutritional profile as
• Refeeding syndrome occurs due to hormonal and
metabolic response to feeding
the traditional F-100 milk-based diet.
• The biochemical hallmark of this condition is
• RUTF are commonly used in inpatient therapeutic
hypophosphataemia.
feeding regimen
• Supplementing high amount of proteins in severely
• RUTF are often made from peanuts, oil, sugar, and
malnourished child is a huge risk factor.
milk powder
• Manifests during the initial stages of refeeding
• Recommended by WHO and UNICEF for
management of children with SAM without
• Commonly seen with total parenteral nutrition (TPN)
and rarely with enteral feeds
complications.
• Fluid and electrolyte abnormalities
• For community management of SAM children.
j Abnormalities in fluid balance
• High energy therapeutic food is provided on an
j Hyperglycemia/hypoglycemia
outpatient basis
j Vitamin and micronutrient deficiencies
• Milk products provide around 50% of the total
j Hypophosphatemia, hypomagnesemia,
proteins.
hypokalemia
• Amongst children with SAM, those requiring hospital
admission are only those with complications. Studies Features
have shown that home-based management with • Abdominal distension, ascites, hepatomegaly
Ready-to-Use Therapeutic Food (RUTF) is better than • Parotid swelling, hypertrichosis, gynecomastia
hospital treatment in children with SAM without • Eosinophilia, splenomegaly, hyper estrogenic state.
complications.
• Composition:
j Milk powder
j Vegetable oils 4.7 Vitamin deficiencies
j Peanuts
Sugar
4.7.1 Vitamin A deficiency
j
j Minerals
j Vitamins Pathophysiology:
j Roasted groundnuts • Naturally occurring retinoids include retinol, retinyl
• The ingredients are ground, mixed and amalgamated palmitate, retinal, and retinoic acid (most active).
to make a paste with reduced particle size (<200 • Body obtains Vitamin in two forms—preformed
micron). vitamin A and provitamin A.
• Can be safely given to SAM children above 6 months • Vitamin A is stored in the liver where unesterified
of age. retinol binds to retinol binding protein (RBP).
47
mebooksfree.com
Functions
• Vision: Retinal forms the prosthetic group of visual
proteins Rhodopsin and Iodopsin. Also, Vitamin A is
essential to maintain corneal stroma and conjunctival
mucosa.
• Resistance to infections: Also known as the anti-
infective vitamin. Vitamin A deficiency leads to
depression of both humoral and cell mediated
immunity. Retinoic acid is responsible for
development and differentiation of white blood cells
especially T lymphocytes.
• Epithelial cell integrity: Essential for integrity of skin Figure 4.4 Bitot spot.
and mucosal cells of respiratory, digestive and urinary
tract. Vitamin A deficiency leads to destruction of first the first clinical sign. Bitot spots (Fig. 4.4) are the
line of defense of the body. most characteristic feature. They appear as triangular
• Growth and development: Retinoic acid is needed area on the temporal aspects of junction of cornea and
for development of heart, limbs, eyes and ears during sclera. Corneal xerosis sets in leading to blindness.
the embryonic period. Retinoic acid is also present in
the brain and is associated with synaptic plasticity of WHO classification
the hippocampus. Primary signs Secondary signs
• Antineoplastic activity: Vitamin A has a preventive role
in cancers of mouth, skin, bladder, lung and breast. X1A Conjunctival XN Night
• Antioxidant: Vitamin A and its precursors also act as xerosis blindness
antioxidants. X1B Bitot spots XF Fundal
Sources changes
• Breastmilk supplies the requirement of vitamin A for X2 Corneal xerosis XS Corneal
the first 6 months of life. scarring
• Pre formed retinol is present in fish liver oil, egg yolk X3A Corneal ul-
and dairy products. ceration(<1/3 of
• Vegetable sources: Green leafy vegetables, carrots, cornea)
papaya, mango, and spinach. X3B Corneal ul-
• Liver is the richest dietary source. ceration(>1/3 of
Causes of deficiency: cornea)
• Vitamin A is not synthesized in the body
• Deficiency can be secondary to malnutrition, defective Treatment:
absorption, defective metabolism or increased
requirement. Three doses of Vitamin A are given; first dose imme-
• Inadequate breastfeeding is prime cause in first diately on diagnosis, second dose 24 h later and third
6 months of life. dose 1–4 weeks later.
• Requirement is increased in preterms and in < 6 months 50,000 IU
infections like measles. 6–12 months 1 lac IU
• Zinc deficiency also increases the risk of vitamin A >12 months 2 lac IU
deficiency.
RDA of Vitamin A (in retinol equivalents)
Infants 350 mg/d Severe PEM: repeat monthly doses of vitamin A till PEM
resolves
Children 400 mg/d
Prevention and Control:
Adolescents and adults 600 mg/d Prevention is achieved by:
Pregnancy 800 mg/d
• Improving consumption and availability of Vitamin A.
Lactating women 950 microgram/d • Food fortification.
• Periodic megadose Vitamin A supplementation to
Clinical features: preschool children and during pregnancy.
• Subclinical deficiency is generally missed. First To healthy children:
and most characteristic early clinical feature is • Vitamin A first dose of 1 lac IU, subcutaneously at
Xerophthalmia. Xerosis of the conjunctiva is generally 9 months along with Measles vaccine
48
mebooksfree.com
• Vitamin A 2nd at 16 months (2 lac IU, Orally). Then

one dose (2 lac IU, Orally) every 6 months up to the
age of 5 years.
During pregnancy and neonates:
• A dietary or supplementary increase of 10,000 IU/day
in pregnancy
Breastfed neonates do not require additional supple-
mentation.
4.7.2 Nutritional Rickets

Etiopathogenesis:
• Rickets is a disease of the growth plate characterized
by deficient mineralization.
• This basically leads to inadequate mineralisation of
osteoid leading to skeletal deformities.
• As it is a disorder of growing bones, it invariably
presents by 18 months of age.
Staging of vitamin D deficiency:
• Stage I: Vitamin D deficiency leads to decreased
intestinal calcium absorption leading to
hypocalcemia. Hypocalcemia leads to secondary
hyper parathyroidism, which mobilises calcium,
Figure 4.5 Active rickets.
increases renal absorption of calcium and up
regulates renal 23-hydroxy Vitamin D and 1-alpha-
hydroxylase. Radiological features (Fig. 4.5)
• Stage II: Calcium normalizes, PTH, and AlPO4 are • Rachitic changes are easily appreciated on X-ray wrist
elevated. Physeal manifestations of rickets become • Reduced calcification results in growth plate thickening
apparent, both clinical and radiological. • Fraying—the edge of the metaphysis loses its sharp
• Stage III: With worsening Vitamin D deficiency, there border
is decreased intestinal calcium absorption leading to • Cupping The distal edge of the metaphysis
florid clinical and radiographic features of rickets. transforms from a convex or flat into a more
concave. This finding is seen at the distal ends of
Clinical Features
long bones.
Head: Chest: • Coarse trabeculation of the diaphysis
• Craniotabes • Rachitic rosary/Harrison • Generalized rarefaction.
• Frontal bossing sulcus • Increased distance between epiphysis to metaphysis
• Delayed fontanel • Respiratory infections
Treatment
closure and atelectasis
Vitamin D dosage
• Delayed dentition
• Craniosynostosis
Spine and extremities General Age Daily regi- Weekly Reg- Stoss Mainte-
• Scoliosis • FTT group men (8–12 imen 8–12 therapy nance
• Kyphosis/Lordosis • Listlessness weeks) weeks) dose
• Enlarged wrist and • Protruding abdomen <1 1,000 IU 50,000 IU Not 400–
ankle • Fractures month recom- 1,000 IU
*Windswept deformity • Muscle weakness mended
• Bowing of tibia/fibula (proximal)
1–12 1,000– 50,000 IU 1–6 lakhs 400–
• Coxa vara • Hypocalcemic symptoms
month 5,000 IU over 5 days 1,000 IU
1–18 5,000 IU 50,000 IU 3–6 lakhs 600–
Diagnosis years units 1–5 1,000 IU
• Most are diagnosed by classical radiological features— days oral
cupping, splaying and flaying of the metaphysis
• Diagnosis is supported by a detailed history, an extensive • Treatment should be continued till there is
clinical examination and laboratory test results. biochemical evidence of recovery and radiographic
49
mebooksfree.com
evidence of healing, which usually occurs by Vitamin K deficiency bleeding (Previously known as
12 weeks. Skeletal deformities also diminish with Hemorrhagic disease of newborn –HDN):
appropriate therapy. • Classic VKDB
j Occurs in 1–14 days of age
Causes:
4.7.3 Vitamin E deficiency
j
– Poor transplacental transfer

– Inadequate intake during first few days of life
• Vitamin E includes all stereoisomers of tocopherols and
tocotrienols. – Absence of intestinal synthesis due to gut
Functions of Vitamin E sterility
– Seen exclusively in breastfed infants due to low
• Chain-breaking antioxidant
breastmilk content of Vitamin K
• Pyroxyl radical scavenger that protects LDLs and
polyunsaturated fats in membranes from oxidation. j Mainly presents as GI tract bleed or mucosal bleed
or umbilical stump bleed or post circumcision site
• Also inhibits prostaglandin synthesis, protein kinase C
and phospholipase A2 bleed.
• Early onset VKDB
Requirement j Presents at birth or immediately after
• The RDA for vitamin E is 15 mg/d (34.9 mol or j Caused by maternal intake of drugs like Warfarin
22.5 IU) for all adults. and Phenobarbitone.
• Isolated dietary deficiency of vitamin E is extremely • Late VKDB
rare j Occurs from 2–12 weeks of age
• Vitamin E deficiency is seen along with certain j Causes:
diseases – Chronic liver disease
j Prolonged malabsorptive state – Malabsorption as in cholestatic liver diseases,
j Cystic fibrosis biliary atresia and cystic fibrosis.
j Prolonged cholestasis – Receiving prolonged antibiotics is a risk factor
j Celiac disease j Mainly presents as Intracranial Bleed.
Clinical Features
Laboratory Findings:
• Axonal degeneration of the large myelinated axons • Prothrombin time (PT) is prolonged.
• Areflexia, Ataxic gait, Decreased vibration and position • Partial thromboplastin time is usually prolonged
sensations.
but may be normal during early stages as factor
• Peripheral neuropathy, Posterior column and 7 has the shortest half-life and does not affect
spinocerebellar symptoms
aPTT.
• Ophthalmoplegia, Pigmented retinopathy • Platelet count is normal
• Hemolytic anemia, Skeletal myopathy • Fibrinogen levels are normal
Laboratory diagnosis • In early deficiency, PT is normal, but there is
• Reduced blood levels of Tocopherol (<5 g/mL, or elevation in undercarboxylated forms of proteins
<0.8 mg of tocopherol per gram of total lipids) that are normally carboxylated in presence of
Treatment Vitamin K. Determination of levels of Proteins
• Children with symptomatic vitamin E deficiency are Induced by Vitamin K Absence (PIVKA) can detect
treated with 400 mg/d of tocopherol. early deficiency.
• Children with abetalipoproteinemia need high doses- Treatment:
5000–7000 mg/d. • Infants should be given 1–3 mg of parenteral Vitamin
K and PT should normalize within 24 h.
4.7.4 Vitamin K deficiency • In adolescents, 2.5mg to 10mg of stat dose can be
given.
Vitamin K—Fat soluble Vitamin • In cases of life threatening bleeds, immediate Fresh
• Cofactor for gamma glutamyl carboxylase, Frozen Plasma (FFP) transfusion can restore clotting
an enzyme responsible for post translational factors and improve coagulopathy.
carboxylation Prevention:
• Necessary for synthesis of clotting factors II, VII, • Administration of Vitamin K soon after birth
IX, X (procoagulants), protein C and protein S prevents early VKD but doesn’t prevent late
(Anticoagulants) VKDB.
• Deficiency results in clinically significant bleeding • Discontinuing the offending medication soon before
and bone problems delivery can prevent secondary VKDB.
50
mebooksfree.com
4.7.5 Thiamine deficiency • Not only a disease of chronic alcoholics but also in
malnourished children.
Thiamine (B1)—water-soluble vitamin
Diagnosis:
• Active form- Thiamine diphosphate • Diagnosis is mainly clinical
• Cofactor for enzymes like pyruvate dehydrogenase, • Objective diagnosis: Low erythrocyte transketolase
transketolase, and alpha ketoglutarate activity with high thiamine pyrophosphate effect.
• Major role in carbohydrate metabolism (HMP • MRI changes include bilateral symmetric hyperintense
shunt), nucleic acid synthesis, and nerve conduction areas in basal ganglia and frontal lobe.
(synthesis of GABA and Ach).
Treatment
Dietary sources • Children with cardiac/neurologic manifestations are
• Present in both vegetarian and non vegetarian diets. treated with 10 mg IV/IM thiamine daily for 1 week
Deficiency (when intake <1 mg/day): followed by 3–5 mg thiamine orally per day for
• Causes 6 weeks.
j Malnutrition • Cardiac symptoms subside quickly; neurological
j Malignancy symptoms take long time and may not even
j Following surgery completely regress.
j Blind loop/short bowel syndrome
j Polished rice consumers 4.7.6 Riboflavin Deficiency
j Alcoholics
• Clinical features Riboflavin (B2) - water soluble vitamin
Early • Part of coenzymes like Flavin Adenine Dinucleotide
j Apathy, irritability, confusion (FAD) and Flavin Mono Nucleotide (FMN)
j Depression, drowsiness, and nausea • Major role in redox reactions in Electron Transport
Established beriberi Chain (ETC)
Peripheral neuritis manifesting as tingling,
Deficiency:
j
burning, parasthesias
• Causes:
j Tenderness and cramping of muscles
j Malnutrition, Malabsorptive states
j Psychological disturbances
j Drugs like OCPs and phenothiazines
Optic nerve atrophy
Phototherapy, Complex II deficiency
j
j
Hoarseness of voice (Laryngeal nerve involvement)
• Clinical features
j
Late: j Cheilosis glossitis, angular stomatitis

j Raised ICT
j Conjunctivitis, photophobia, and lacrimation
j Meningismus
j Seborrheic dermatitis, corneal neovascularization
Coma
• Diagnosis:
j
• Types of BeriBeri (depending upon the amount of j Mainly clinical

fluid accumulation)
j Response to therapy is diagnostic
j Dry type (neuritic type)
j Objective diagnosis: High Erythrocyte Glutathione
– Peripheral neuropathy with symmetric motor
Reductase (EGR) activity coefficient with a low
and sensory function loss.
urinary riboflavin excretion.
– Distal involvement is more
• Treatment:
– Psychiatric disturbances may be seen
j 3–10 mg/day of riboflavin orally for 3–6 months
j Wet type(cardiac type)
with a well balanced diet.
– Characterised by edema, cardiomegaly and
CCF.
– Secondary to fatty degeneration of the 4.7.7 Niacin deficiency (Vitamin B3)
myocardium.
– Supplementation quickly reverses symptoms. • Deficiency leads to clinical syndrome called Pellagra
j Infantile beriberi Risk factors
– Characterised by dyspnea, cyanosis and • Prolonged antibiotic use
cardiomegaly. • Hartnup disease
– Can present with seizures. • Carcinoid syndrome
– May be fatal if untreated. Clinical features.
Wernicke Encephalopathy • Early symptoms include loss of appetite, generalized
• Triad of ophthalmoplegia, ataxia and mental changes. weakness, irritability, abdominal pain and vomiting
51
mebooksfree.com
• Classic 4D symptoms seen in pellagra Deficiency:

Dermatitis - Characteristic skin rash that is
j • Causes:
pigmented and scaling, particularly in skin areas j Strict vegetarian/vegan diet
exposed to sunlight. Casal’s necklace—Rash forms j Breastfed infants of deficient mothers
a ring around the neck. j Malabsorption
j Diarrhea (due to proctitis and malabsorption) j Drugs like PPI and H2 antihistaminics
j Dementia • Clinical manifestations:
j Death j Neurological features like irritability, hypotonia
• Other features include bright red glossitis, vaginitis, and developmental delay
esophagitis, depression, and seizures j Sensory deficits like parasthesias, peripheral neuritis.
j Megaloblastic anemia and Knuckle hyper
pigmentation.
4.7.8 Vitamin B6 deficiency j Subacute combined degeneration of cord
• Vitamin B6 is present in forms like pyridoxine, pyridoxal, Treatment and Prevention:
pyridoxamine, and their phosphorylated forms • Severe Deficiency: IV/IM 250–1000 mcg Vitamin B12,
• Coenzymes for amino acid metabolism, heme repeated daily for 1 week, followed by weekly doses
synthesis, neurotransmitter synthesis, glycogen for 1 month.
metabolism and steroid action • Mild To Moderate Deficiency: It may be treated with
• Active form: Pyridoxal 5 phosphate lower oral dose
Dietary sources • Neurologic symptoms take around a month to
• Found in pulses, cereals, meats, fruits and vegetables. disappear but sensory symptoms might take upto
• Also derived from intestinal flora. 6 months or more
Deficiency:
• Causes: 4.7.10 Vitamin C deficiency (Scurvy)
j High protein diet
j Drug intake like isoniazid, peniciallamine, OCPs • Ascorbic acid plays an important role in synthesis of
• Clinical Features: collagen-
j Irritability, convulsions (pyridoxine dependent j Hydroxylation of proline and lysine
seizure syndrome) j Wound healing
j Hypochromic anemia, peripheral neuritis j Role in cholesterol metabolism, neurotransmitter
j Oxalate calculi, failure to thrive metabolism and synthesis of carnitine
• Diagnosis: j Important role in iron absorption
j Mainly clinical j Antioxidant role
Objective tests: Low erythrocyte transaminase, low
Dietary sources: Green leafy vegetables, Capsicum
j
glutamic pyruvic transaminase, high xanthurenic

Green chillies, Amla, Guava, and Lemon
acid excretion after ingestion of tryphtophan.
Deficiency:
• Prevention and Treatment: • Causes:
Parboiling of rice
Children receiving heat treated milk or unfortified
j
j
IV/IM 100 mg Pyridoxine in vitamin B6 deficiency
formula feeds
j
seizures
j Children not receiving fruits or fruit juices
2–10mg IM or 10–100 mg per orally per day in
• Clinical features:
j
pyridoxine dependent children

a) Early:
– Irritability
4.7.9 Vitamin B12 deficiency – Loss of appetite
– Low grade fever
• Active form is 5-deoxyadenosyl cobalamine. – Pseudoparalysis due to knee and ankle swelling
• Cofactor in enzymes for carbohydrate and lipid b) Late:
metabolism. – Scorbotic rosaries (wedge shaped) at
• Helps in protein and nucleic acid synthesis. costochondral junctions with sternal depression
• Hence, important for myelination, hematopoiesis, – Gum changes like blue purplish discoloration
and psychomotor development. with swelling
Absorption: – Anemia due to impaired iron absorption
• Intrinsic factor (IF) protein, synthesized in the – Hemorrhagic manifestations like gum
stomach, is required for B12 absorption in the ileum bleeding, petechiae, purpura, and ecchymoses
• Some amount is absorbed through passive diffusion. at pressure points, poor wound healing.
52
mebooksfree.com
• Treatment:
j 100–200 mg/day orally or parenterally for
3 months
j Milk fortification with Vitamin C
4.7.11 Copper
• Absorbed via specific intestinal transporter
• Circulating form is bound to ceruloplasmin
• Enzyme cofactor (cytochrome oxidase superoxide
dismutase and enzymes involved in iron metabolism)
• Helps in utilization of iron stores
• Deficiency is seen in PEM, malabsorption, Prolonged
‘total parenteral nutrition’ and prematurity
• Deficiency features
j Osteoporosis, Metaphyseal fraying, fractures
Figure 4.6 Radiographic features of Scurvy. j Microcytic anemia, Neutropenia
j Depigmentation of hair and skin
j Neurologic symptoms
Diagnosis: j Immunodeficiency
• Radiological findings (Fig. 4.6):
j Ground glass appearance of diaphysis 4.7.12 Zinc
Pencil outlining of epiphyses and diaphysis.
j
• Cofactor of enzymes (Alkaline phosphatase carbonic
j A zone of well calcified cartilage at metaphysis— anhydrase and pancreatic carboxypeptidase)
White line of Frenkel
• Regulated gene transcription (Zinc-finger proteins)
Zone of rarefaction under the white line of
j
• Dietary sources: Meat, liver, fish, nuts, grains and legumes.
Frenkel—Trummerfeld Zone
• Seen in PEM, malabsorption, connective tissue diseases,
j Pelkan Spur Prolonged TPN
• Biochemical tests: • Deficiency features
j Not very useful j Growth retardation, Anemia, Hepatosplenomegaly
j Leukocyte Vitamin C concentration is a good j Periorifical and extremity Dermatitis
indicator—Difficult to perform j Immunodeficiency, Impaired wound healing
j Urinary excretion of vitamin after ascorbic acid test j Hypogonadism, Loose stools
dose j Dry keratotic skin, infantile tremor syndrome
4.8 Trace Elements—Physiology and Deficiency
Element Physiology Effects of deficiency Toxicity

Fluoride • Incorporated into bone and • Dental caries • Fluorosis
teeth
Iodine • Component of thyroid • Hypothyroidism • Goiter
hormone • Elevated TSH and underactive
thyroid
Iron • Component of hemoglobin, • Anemia • Diabetes
myoglobin, cytochromes, and • Decreased alertness • Neuro-psychiatric diseases
other enzymes • Impaired learning • Malignancy
Manganese • Cofactor of enzymes (superox- • Growth retardation, Decreased • Cholestasis
ide dismutase) clotting proteins • Encephalopathy
• Hypocholesterolemia, Weight • Cardiomyopathy
loss
53
mebooksfree.com
Element Physiology Effects of deficiency Toxicity

Molybde- • Enzyme cofactor (xanthine • Tachycardia, Tachypnea • Unmask gout
num oxidase ) • Night blindness, Central scotoma • Bone defects like genu valgum
• Irritability, Coma
• Upper GI malignancy
Selenium • Enzyme cofactor—Glutathione • Cardiomyopathy (Keshan dis- • Dental caries
peroxidase (prevents oxidative ease) • Alopecia
damage) • Myopathy, arthritis
• Antioxidant • Liver necrosis
Cobalt • Part of Vitamin B12 complex • Anemia • Cardiomyopathy
• Required for iodine utilization • Goiter
Chromium • Stimulates the action of • Impaired glucose tolerance • Dermatitis
insulin • Encephalopathy • Renal failure
• Peripheral neuropathy

Please visit MedEnact to access chapter wise MCQs and
previous year pediatrics theory questions asked in various
final MBBS University examinations.
54
mebooksfree.com
Fetal and neonatal medicine
5.1 Fetal assessment and prenatal Parameter Accuracy in estimation

Trimester used for GA of gestational age
diagnosis
I Crown-rump +/-1 week
length (CRL)
5.1.1 Assessment of gestational
II BPD, HC, AC, FL +j-2 weeks
age
III BPD, HC, AC, FL +/-3 weeks
• Importance of accurate estimation of gestational age
• To plan elective diagnostic procedures
like chorionic villus sampling (CVS) and
amniocentesis
5.1.2 Prenatal diagnosis of fetal
• To decide on the plan of management in preterm disease
labor as the prognosis and postnatal complications Maternal serum a-fetoprotein (MSAFP) estimation
depend on the gestational age • Estimated between 15 to 22 weeks gestation
• For induction of labor and elective caesarean • Elevated MSAFP above 2.5 multiples of the median
section to prevent iatrogenic prematurity for gestation age is a positive screening test for neural
Methods for assessment of gestational age ( GA) tube defects (NTD)
A) History Ultrasonography-
• Nagele's rule • May reveal intracranial signs secondary to NTDs like
- Calculated from Last Menstrual Period (LMP) • Change in head shape (lemon sign)
- Calculated by adding one year, subtracting three • Deformation of the cerebellum (banana sign)
months, and adding seven days to the LMP.
- The Estimated delivery date is approximately First-trimester screening
280 days (40 weeks) from LMP • Pregnancy -associated plasma protein-A (PAPP-A)
• From the date of quickening ( maternal perception
levels are reduced and hCG levels are increased
of fetal movements for the first time) pregnancies with trisomy 21.
B) Clinical examination • First-trimester nuchal translucency screening -
• Estimation the fundal height of uterus
Ultrasound assessment of the fluid collected at the nape
• Auscultation of fetal heart sounds-Appears at
of the fetal neck is a sensitive marker for aneuploidy
18 - 20 weeks • Combined first-trimester screening-Combination
C) Investigation - of the two maternal serum markers (PAPP-A and
• Ultrasound is the most accurate method for
~-hCG) and nuchal translucency measurements and
estimating gestational age maternal age detects 80% of trisomy 21 fetuses
• The accuracy of gestational age estimated Second-trimester aneuploidy screening
by biometry decreases with increasing • Low levels of MSAFP are associated with
gestational age chromosomal abnormalities.
55
• Trisomy 21— • Biochemical tests of the amniotic fluid (L/S ratio)

HCG and inhibin levels are increased
j help in assessment of fetal lung maturity.
j MSAFP and unconjugated estriol levels are decreased. • Fetal cells can be extracted from the fluid sample and
• Trisomy 18 - analyzed for chromosomal and genetic makeup which
j Low levels of all markers (MSAFP, hCG, uE3, helps in diagnosis of many diseases. e.g., α-thalassemia,
inhibin) Duchenne muscular dystrophy, cystic fibrosis
A) Chorionic Villus Sampling (CVS) C) Percutaneous Umbilical Blood Sampling (PUBS)
Procedure Procedure—Can be performed under ultrasonic guid-
• Under ultrasound guidance, a sample of placental ance from the second trimester until term.
tissue is obtained through a catheter through Complications
transcervical or transabdominal approach • 1% to 2% risk of fetal loss
• Performed at or after 10 weeks gestation—earliest • Risk of Preterm delivery in 5%.
possible detection of a genetically abnormal fetus
Uses
through analysis of trophoblast cells.
• Provides diagnostic samples for cytogenetic,
Complications hematologic, immunologic, or DNA studies
• Pregnancy loss rate −0.5% to 1.0%. • It can provide access for in utero treatment.
• CVS performed before 10 weeks of gestation is D) Preimplantation Biopsy or Preimplantation Genetic
associated with an increased risk of
Diagnosis (PGD)
j Fetal limb-reduction defects
j Oromandibular malformations.
• Procedure—During an in vitro fertilization process,
in early gestation at the eight cell stage, prior to
Analysis of trophoblasts transfer, one or two cells are removed for analysis.
• If direct preparations of rapidly dividing Uses
cytotrophoblasts are done—full karyotype analysis is
available in 2 days.
• PGD is used to identify a wide range of autosomal
recessive, dominant, and X- linked molecular
• If trophoblast cells are cultured, which are diagnoses.
embryologically closer to the fetus—additional
8–12 days are required for analysis
• For couples at risk for a chromosomally abnormal
conception, testing allows for identification of
• If a mosaic diagnosis is made on CVS analysis - embryos that carry the disorder in question, and
amniocentesis is performed as a follow-up study to
transfer of unaffected embryos can occur.
analyze fetal cells.
B) Amniocentesis 5.1.3.1 Cell free fetal DNA in the maternal
Procedure
circulation
• Ultrasound guided needle is used to remove amniotic
fluid from around the fetus. The removed amniotic • Fetal cells in the maternal circulation can be separated
fluid (20 mL) is replaced by the fetus within 24 h. and analyzed, but the limited number of cells obtained
• Early amniocentesis (<13 weeks) —Performed at 10 precludes using this technique on a clinical basis.
to 14 weeks gestation Uses
• Second trimester amniocentesis—Performed at • Cell-free fetal DNA techniques are available for
16–20 weeks identification of fetal Rh status in women at risk for
Complications isoimmunization.
• Pregnancy loss—1% to 2% in early amniocentesis • This technique is currently under research for
and 0.5% to 1% in late amniocentesis identification of fetuses at risk for single-gene disorders
• Increased incidence of clubfoot in early
amniocentesis.
5.1.3 Fetal size and growth rate
Uses
• Amniotic fluid can be analyzed for a number of abnormalities
compounds, including alpha-fetoprotein (AFP), • Fetal growth assessment is important for assessing
acetylcholinesterase (AChE), bilirubin, and perinatal prognosis and to plan perinatal treatment.
pulmonary surfactant.
j Increased levels of AFP along with the presence of
AChE—98% sensitivity in identifying NTDs 5.1.3.1 Fetal growth restriction (FGR)
j AFP levels are elevated in fetuses with abdominal Definition of FGR–
wall defects, congenital nephrosis, or intestinal • Fetuses weighing <10th percentile for gestational age
atresias with pathological restriction in growth
56
mebooksfree.com
Fetal and neonatal medicine Chapter |5|
Causes 5.1.4.2 The nonstress test (NST)

Extrinsic causes Intrinsic causes • NST is a reliable means of fetal evaluation.
• It is simple to perform, relatively quick and
• Uteroplacental • Chromosomal noninvasive
insufficiency abnormalities
• No discomfort or risk to mother and fetus.
• Severe PIH, • Congenital
Preeclampsia malformations Principle
• Gestational diabetes • Congenital infections • Fetal activity results in a reflex acceleration in heart
• Maternal under- (TORCH) rate.
nutrition • Absence of accelerations in a fetus who previously
• Maternal infection demonstrated them indicates fetal hypoxia.
• Maternal drug abuse • NST reflects the current fetal state and cannot predict
future events or neonatal outcome.
Diagnosis of FGR Procedure
• Maternal clinical examination • The fetal heart rate (FHR) is monitored through
• Ultrasonography improves the sensitivity and skin electrodes on the maternal abdomen and
specificity to >80%. uterine activity is simultaneously recorded through a
j FGR may be diagnosed when a fetal biometry is tocodynamometer.
<10th percentile Interpretations
j Signs of a compromised intrauterine environment
such as oligohydramnios, an elevated head- Reactive NST Nonreactive NST
abdomen ratio or abnormal Doppler velocimetry
• Heart rate between 110 • Defined as less than
in the umbilical cord. and 160 bpm two accelerations in
j Serial scans documenting absent or poor • Normal beat-to-beat 40 min.
intrauterine growth regardless of the weight variability (5 bpm) • A nonreactive test is
percentile • Two accelerations of generally repeated
at least 15 bpm lasting once to confirm the
5.1.3.2 Macrosomia for atleast 15 s within findings
a 20 min period.
• Macrosomic fetuses (>4000 g)
• At increased risk for shoulder dystocia and traumatic
birth injury. Significance
• Causes— • The chance of fetal demise within a week of a reactive
j Maternal diabetes NST is approximately 3 per 1000.
j Post-term pregnancy • Negative predictive values for stillbirth within 1 week
j Genetic overgrowth syndromes of reactive NST is 99.8%.
j Maternal obesity • The NST is usually done on a weekly basis, although
increased testing (2 times per week to daily testing) is
recommended in high-risk cases
5.1.4 Antepartum assessment
of fetal well-being
5.1.4.1 Fetal movement count 5.1.4.3 Contraction stress test (CST)
• Simplest method of fetal assessment • CST is now used less commonly with the
availability of multiple other modalities for fetal
• Fetuses normally have a sleep–wake cycle, and
mothers generally perceive a diurnal variation in fetal surveillance
activity. Principle
• Periods of inactivity >1 h are unusual in a healthy • Pressure generated during uterine contractions
fetus and should alert the physician to the possibility can briefly reduce perfusion of the intervillous
of fetal compromise. space.
• A “count to 10” method by the mother has been • A healthy fetoplacental unit has sufficient
validated and evaluated as a screening test. reserve to tolerate this short reduction in oxygen
• The same time of day is chosen and fetal movements supply.
are noted upto perception of 10 fetal movements. • However, in an unhealthy fetus, respiratory reserve
• Lack of perception of 10 movements within a 12 h may be so compromised that the reduction in oxygen
time period requires further evaluation. supply results in fetal hypoxia.
57
mebooksfree.com
Procedure j A reactive NST

• Similar to NST, CST monitors FHR and uterine j Amniotic fluid volume (vertical fluid pocket >2 cm)
contractions. j Fetal breathing movements
• If there are no spontaneous contractions, contractions j Fetal activity
can be induced with intravenous oxytocin, which is
j Fetal tone.
called as oxytocin challenge test.
• A modified BPP includes assessment of NST (acute
• Uterine contractions are considered to be effective if stress) and amniotic fluid volume (chronic stress).
there are 3 contractions each lasting 40 to 60 s within
a 10-min interval.
• The total score determines the course of action.
• Reassuring tests (8 to 10) are repeated at weekly
Interpretation intervals
Late Under hypoxic conditions FHR • Less reassuring results (4 to 6) are repeated later the
deceleration begins to decelerate 15 to 30 s same day
after onset of the contraction, • Very low scores (0 to 2) generally prompt delivery.
reaches its nadir after the peak Significance
of the contraction, and does • The chance of stillbirth fetus within 1 week of a
not return to baseline until after reassuring test is approximately 0.6 to 0.7 per 1000.
the contraction ends. This heart • Negative predictive value for stillbirth within 1 week
rate pattern is known as a late of a reassuring BPP, modified BPP and negative CST is
deceleration >99.9%.
Positive CST If late Decelerations are
consistently seen in association
with contractions. 5.1.4.5 Doppler ultrasonography
Negative CST If at least three contractions of at of fetal vessels
least 40 s each occur within a 10 Umbilical artery doppler
min period without associated • Fetal umbilical artery blood flow is a noninvasive
late decelerations. technique to assess placental resistance.
Suspicious CST If there are occasional or • Poorly functioning placenta has an increased
inconsistent late decelerations. resistance to flow that is particularly noticeable in
Unsatisfactory If contractions cannot be fetal diastole.
CST stimulated or a satisfactory FHR • It is the primary surveillance tool for pregnancies with
tracing cannot be obtained. intrauterine growth restriction
Hyperstimulated If contractions occur more • The commonly used indices of flow are
CST frequently than every 2 min j Systolic: diastolic ratio (S/D)
or last longer than 90 s, it is j Resistance index (S-D/S)
considered as a hyperstimulation j Pulsatility index (S- D/mean)
and test cannot be interpreted. • Umbilical artery Doppler velocimetry measurements
improves perinatal outcomes in IUGR babies
Significance
Middle cerebral artery doppler
• A negative CST is even more reassuring than a reactive
NST - the chance of fetal demise within a week of a • Measurements can also be used in the assessment of
negative CST is 0.4 per 1000. the fetus that is at risk for either FGR or anemia.
• If a positive CST follows a nonreactive NST, the risk Ductus venosus doppler
of stillbirth is 88 per 1000 and the risk of neonatal • Reveals progression or worsening of uteroplacental
mortality is 88 per 1000. insufficiency
• One third of patients with a positive CST will require • Absent or reversal of end-diastolic flow through this
cesarean section for persistent late decelerations in vessel is considered as a terminal stage and indicates
labor. imminent fetal demise.
5.1.5 Indications for antepartum

5.1.4.4 Biophysical profile (BPP)– fetal surveillance
• It combines NST with other parameters determined • Pregnancies with increased risk for stillbirth like
by ultrasound examination. j Chronic hypertension
• A score of 0 or 2 is assigned for the absence or j Pre-gestational diabetes and poorly controlled
presence of each of the following gestational diabetes
58
mebooksfree.com
Growth restriction
j – Symmetric in shape and closely mirror uterine
Advanced maternal age
j contractions in time of onset, duration and
j Maternal vascular disease ending.
• Fetal surveillance tests are usually begun at 32 weeks – These decelerations are due to fetal head
although in the setting of FGR, initiation prior to compression in the pelvis
32 weeks is often undertaken. j Late decelerations
• The frequency of monitoring is typically weekly, – The onset, nadir, and recovery of the
although in high-risk conditions monitoring will deceleration occur after the beginning, peak,
often occur more frequently. and end of the contraction, respectively.
– Late decelerations are due to uteroplacental
insufficiency and possible fetal hypoxia.
5.1.6 Intrapartum assessment Repetitive late decelerations demand action.
of fetal well-being j Variable decelerations
The FHR can be monitored during labor by one of follow- – Vary in shape and timing in relative to
ing methods contractions.
– Usually due to fetal umbilical cord
• Noninvasive methods—auscultation with compression.
stethoscope, ultrasound monitoring and surface-
electrode monitoring (cardiotocography CTG) from
the maternal abdomen 5.1.6.2 Fetal blood gas analysis
• Invasive method—a small electrode is placed into • A fetal scalp blood sample for fetal blood gas analysis
the skin of the fetal presenting part to record the fetal may be obtained to confirm or dismiss suspicion of
electrocardiogram directly. It is the most accurate fetal hypoxia.
method • An intrapartum scalp pH >7.20 with a base deficit
<6 mmol/L is normal.
5.1.6.1 Parameters of the fetal heart rate
that are evaluated include
A) Baseline Heart Rate 5.2 Important terminologies
Normal basal heart rate is between 110 and
and definitions in neonatology
j
160 bpm
B) Fetal bradycardia
j Defined as an FHR <110 bpm • Live birth: A product of conception irrespective
j Causes of weight or gestational age that after separation
– Fetal Congenital heart block from mother, shows any evidence of life, such as
– Maternal systemic lupus erythematosus. breathing, heartbeat, pulsation of umbilical cord or
C) Baseline tachycardia definite movement of voluntary muscle.
j Defined as an FHR >160 bpm • Fetal death: Product of conception that, after separation
j Causes from mother, does not show any evidence of life
– Fetal causes—arrhythmias • Still birth (variable definitions):
– Maternal causes—fever, infection, drugs, j Fetal death at a gestational age of 20 weeks or
hyperthyroidism. more or weighing >500 gm (United States)
D) Beat-to-Beat Variability- j For international comparison, WHO defines still
j The autonomic nervous system of a healthy, awake birth as fetal death after 28 completed weeks or
term fetus constantly varies the heart rate from more than 1000 g
beat to beat by 5 to 25 bpm. • Neonatal Period: Birth to 28 days of life
j Causes of reduced beat-to-beat variability j Early Neonatal period—upto 7 days
– Fetal central nervous system depression due to j Late Neonatal period- 7 to 28 days
fetal immaturity, hypoxia, fetal sleep, maternal • Perinatal period: 28th weeks gestation to 7th
medications such as narcotics, sedatives, postnatal day
β-blockers, and intravenous magnesium sulfate. • Classification based on birth-weight (regardless of
E) Accelerations of the FHR are reassuring gestational age)
F) Decelerations of the FHR may be benign or indicative j Low birth weight (LBW)—birth wt. 2.5 kg or less
of fetal compromise depending on the characteristic j Very Low birth weight (VLBW)—Birth wt. ≤1.5 kg
shape and timing in relation to uterine contractions. j Extremely Low birth weight (ELBW)—Birth wt.
j Early decelerations ≤1 kg
59
mebooksfree.com
Antepartum Intrapartum Fetal/Neonatal

factors factors factors
• Maternal age <16 • Fetal distress • Estimated
or >40 years • Breech Wt. <2.5 kg
• Antepartum presentation or >4 kg
hemorrhage • Meconium • Gestational
• Multiple gestation stained Age <37 or
• Poly/ liqour >42 weeks
oligohydramnios • LSCS • SGA/ LGA
• Previous • Forceps baby
history of IUD, delivery • APGAR<4
Figure 5.1 Weight for gestational age—Percentile chart. prematurity, • Chorioam- at 1 min.
Source: Seminars in Perinatology, 2008. IUGR nionitis
Preparing for resuscitation

• Classification based on gestational age • Asphyxia can be anticipated in upto to 50% of
newborn babies based on prior risk factors. In
Preterm birth: <37 completed weeks (259 days)
j
others, it is unexpected. Therefore, it is important to
Term birth : 37–42 weeks (260–294 days)
j
anticipate the need for resuscitation in every delivery
j Post term birth: 42 weeks or more (>=295 days)
and ensure basic readiness to manage asphyxia.
j Past dates: Gestational age >40 weeks
• Classification based on weight for gestational age • Delivery room temperature should be ideally
maintained between 26–28˚C
(Fig. 5.1)
j Small for gestational age (SGA): <2 SD or <10th • At least 1 person with necessary skills for resuscitation
should be present
percentile
j Large for gestational age (LGA): > 2 SD above the • All the equipment must be checked and kept ready
before the anticipated delivery
mean for GA or >90th centile
j Appropriate for gestational age (AGA): Weight Equipment required for Resuscitation
between 10 to 90th centile for that gestational For Ambu Bag
age Ventilation Face Mask (Appropriate sizes)
Laryngoscope—Straight blade (Miller
Mortality indices type)
Endotracheal tubes (Sizes 2.5 to 4)
Perinatal mortality rate: (Still birth + deaths in first
Oxygen tubing with flow meter
week of life) per 1000 live births
Oxygen delivery devices—Nasal mask,
Neonatal Mortality rate: Death of infants in first 28 Nasal prongs, Head box
days of life per 1000 live births.
Suction Suction apparatus
Post neonatal mortality rate: Deaths from 28 days of equipment Suction catheter
life to 1 year of life Bulb suction
Meconium aspirator
Medications Umbilical venous catheterization set
Infant feeding tubes
5.3 Neonatal resuscitation IV catheters
Epinephrine, Naloxone
Normal Saline
• At least 10% of the babies require some form of O negative blood, FFP
resuscitation and <1% require extensive resuscitation
Miscellaneous Radiant warmer
(chest compressions, medications etc.)
Dry linen
• Out of 25 million babies born every year in India, Stethoscope
3%–5% develop asphyxia at birth and require
Gloves
resuscitation. Umbilical cord clamps
High risk pregnancy
• A high-risk pregnancy is defined as the one in which Steps in Neonatal Resuscitation
pregnant mother has an adverse factor evident • Neonatal Resuscitation Program (NRP)
during the course of the pregnancy that can affect the Guidelines—2015 (Fig. 5.2) is currently followed
outcome. worldwide
60
mebooksfree.com
Figure 5.2 Revised updated NRP 2015 Guidelines.
61
mebooksfree.com
• Initial steps include drying, providing warmth, • Adrenaline in Neonatal Resuscitation

positioning the infant, clearing the airway secretions j Used in 1:10000 dilution
followed by evaluation j IV dose: 0.01–0.03 mg/kg (0.1–0.3 ml/kg)
• Evaluation is based primarily on the following two signs: j ET dose: 0.05–0.1 mg/kg (0.5–1 ml/kg)
j Respiration—key to effective neonatal resuscitation. • Administration of naloxone is not recommended as
j Heart rate—the most sensitive indicator of part of initial resuscitative efforts in the delivery room
response to resuscitation. for newborns with respiratory depression.
• A. Airway • Normal saline or Rh negative blood should be used
j Positioning of the neonate for fluid resuscitation in hypovolemia and Ringer
j Suction of mouth followed by nose lactate should be avoided
• B. Breathing: Initiate breathing if no spontaneous Indications for withholding resuscitation:
respirations • If there is no return of heart rate after 10 min of
j Tactile stimulation, such as flicking soles of foot, adequate resuscitation, it is acceptable to discontinue
rubbing the back, etc. resuscitation.
j Positive pressure ventilation (PPV) with a bag and • Babies at a gestational age < 22 weeks
mask or via endotracheal tube • Babies between 22–24 weeks, decision after
• C. Circulation: Maintain the circulation with discussion with caregivers
j Chest compression and medications, if needed. • Congenital malformations (Anencephaly)
j Chest compressions continued for 60 seconds • Trisomy 13
before rechecking heart rate
APGAR SCORE
• Evaluating Color is not recommended as a useful
indicator of oxygenation or effectiveness of • This score was developed by an anaesthesiologist
Virginia Apgar in 1952 to assess effect of obstetric
resuscitation. In the recent guidelines, spO2 is used
anaesthesia on babies.
instead of color evaluation.
• AMBU bag can be used without oxygen /air source but • Objective method of evaluating baby’s condition after
birth
a ‘flow inflating bag’ requires a compressed gas source
• PPV should be attempted immediately if tactile • APGAR stands for A-Appearance (Skin colour),
P-Pulse (Heart Rate), G–Grimacing (Reflex),
stimulation fails. Prolonged tactile stimulation should
A–Activity (Tone) and R-Respiration (Chest movement)
be avoided due to the possibility of ‘secondary apnea’
j Primary apnea- revived with tactile stimulation • APGAR Scoring is done 1 and 5 min after birth,
j Secondary apnea is not revived by tactile • APGAR score is not used to initiate the resuscitation
but to check its response.
stimulation but requires PPV. Absent respiratory
efforts at birth to be considered as secondary • If 5 minute APGAR score is <7, scoring should be
repeated every 5 min till 20 min
apnea and resuscitated.
• Room air resuscitation is done for gestational age > APAR Scoring System
35 weeks
Evaluation 0 point 1 point 2 points
• Supplemental oxygen is used for resuscitating <
35 weeks preterm babies Heart rate 0 <100/min >100/min
• Free flow oxygen is started in a spontaneously Respiration None Irregular, Crying
breathing baby if target saturation is not attained. shallow, gasps
• Routine vigorous suction is not required. Secretions Colour Blue Pale, blue Pink
when excessive can be wiped with cloth extremities
• There is no role for tracheal suctioning in cases of Tone None Weak, passive Active
meconium stained liquor. Babies born out of meconium
Reflex None Facial grimace Active
stained amniotic fluid are said to be vigorous or
response withdrawal
non-vigorous at birth based on heart rate, respiratory
efforts and tone. Even nonvigorous babies need not be
routinely intubated for tracheal suctioning at birth
• Suction pressure should not exceed 100 mmHg
• Ratio of chest compressions to ventilation—3:1 5.4 Birth injuries
(120 events/1 min)
• Delayed cord clamping: Umbilical Cord clamping
should be delayed for atleast 30–60 seconds for
5.4.1 Cephalohematoma
infants not requiring resuscitation • Collection of blood following trauma during birth
• Immediately after birth, preterm neonates <32 weeks • Hemorrhage under the periosteum (Subperiosteal
old should be completely covered in a plastic wrap. location) of the skull bones
62
mebooksfree.com
• Source of bleed: Rupture of subperiosteal blood vessels

• Occurs in 1%−2% of live births.
Clinical features
• Swelling appears after 4−8 h of birth and reaches
maximum size by 3rd day.
• Common sites are parietal bone followed by occipital
and frontal bones.
• Characteristics of Swelling (Fig. 5.3)
j Swelling does not cross the suture line
j Swelling has well-defined margin limited by
suture line.
j Usually unilateral
j Bilateral involvement often associated with
underlying skull fracture.
j Swelling is: fluctuant, irreducible, nonpulsatile in
size during crying.
Natural Course
• Swelling disappears between 2nd week and 3rd Figure 5.4 Caput Succedaneum.
month—depending on its size.
• The lesion becomes a firm, calcified swelling by the
end of 2nd week before getting resorbed. Complications
• Underlying linear skull fracture may be seen in • Risk of jaundice and need for phototherapy
10%−25% of cases • Risk of secondary infection
Treatment
• No specific treatment is required. Resolves 5.4.2 Caput succedaneum
spontaneously over a period of time
• Reassurance to the parents • Serosanguineous fluid collection over the presenting
part between the pericranium and scalp
• This is the swelling of the soft tissue of scalp over
presenting part during vaginal delivery
Clinical features
• Swelling seen at birth
• Diffuse, soft, edematous, pitting, non-fluctuant
(Fig. 5.4)
• Swelling crosses (not limited by) suture lines and
• Disappears spontaneously within 2–4 days of life.
Treatment
• No treatment is required. If extensive ecchymoses are
present,
• Rarely Hyperbilirubinemia may develop requiring
phototherapy.
5.4.3 Subaponeurotic hemorrhage/

subgaleal bleed
• Collection of blood under the aponeurosis in the soft
tissue space that covers the scalp (Fig. 5.5)
• This potential space extends from the orbital ridges
anteriorly to the occiput posteriorly and laterally to
the ears.
• Risk factors
j Vacuum assisted delivery
j Forceps delivery
Figure 5.3 Cephalohematoma. j Hereditary coagulopathy (hemophilia).
63
mebooksfree.com
• Platelets, Prothrombin time, CT and BT

• Serum bilirubin
Treatment
• Mainly Supportive
• Monitoring for signs of shock and prompt and
aggressive therapy
• Parenteral vitamin K injection
• If significant pallor develops, blood transfusion may
be needed
• If baby develops hypotension and shock, rapid
crystalloid infusion and blood transfusion are required.
Complications
• Profound pallor, Shock and Jaundice.
Figure 5.5 Difference between Caput, Cephalhematoma
and Subgaleal hemorrhage. Prognosis
• Overall prognosis is good with careful monitoring
and supportive care and absence of complications like
Clinical features shock
• Diffuse, boggy swelling in the dependent part of the scalp
• Swelling crosses the midline and suture lines
• Swelling is fluctuant and rapidly increases in size after 5.4.4 Brachial palsy
birth Erb’s palsy (C5–C7)
• Superficial bruise, laceration may present • Most common brachial plexus injury
• Hemorrhagic shock can occur due to large volume of • Risk factors: Macrosomic babies, Shoulder dystocia
blood lost. Pallor, tachycardia and hypotension can • Involved hand is adducted, internally rotated, forearm
be present. extended and pronated (Policeman’s or Waiters tip
• Rarely, hypotonia and seizure may present posture) (Fig. 5.6a)
Investigations • Moro’s, biceps and radial reflexes are absent, but
• Serial monitoring of Hemoglobin and Hematocrit grasp reflex is present
• Blood grouping and cross matching • Sensation is variably affected
Figure 5.6 (A) Right sided Erb’s palsy (B) Klumpke palsy.
64
mebooksfree.com
Klumpke’s palsy (C7-C8±1) ventricle, VSD, PDA, Truncus arteriosus and

• Paralyzed hand ± Horner syndrome (Figure 5.6b) Tricuspid atresia
• Weakness of intrinsic muscles of hand and long j CNS malformations include neural tube defects,
flexors of wrist and hand (Claw hand deformity) Caudal regression (Specific for IDM), spinal
• Grasp reflex is absent while Biceps and radial reflexes abnormalities and syringomyelia
are present j Small left colon syndrome—Descending colon,
• Sensory impairment on ulnar aspect of forearm and sigmoid colon and rectum appears smaller than
hand normal. Child presents with bilious emesis and
abdominal distension.
Total brachial plexus palsy
• Prematurity, Intrauterine death
• Complete paralysis of shoulder, arm and hand ± • Macrosomia
Horner syndrome
j Infants have bigger head: chest and shoulder:
• All hand reflexes are absent head ratios, more body fat and visceromegaly. Size
• Absent sensation of all organs except brain increases.
j Hairy pinna, Clefts in thigh, typical cherubic facies
5.4.5 Clavicle fracture j Increased risk of operative deliveries, birth
asphyxia and birth trauma
• Most commonly fractured bone • Metabolic abnormalities
• Etiology j Hypoglycemia (due to postnatal hyperinsulinemia)
j In Vertex presentation-Shoulder dystocia j Hypocalcemia (due to diminished production of
j In Breech presentation-Arm extension parathormone after birth)
• Clinical features j Hypomagnesaemia
j Swelling and redness of skin can be present. • Polycythemia- Increased oxygen consumption
j Decreased spontaneous movement of affected leading to increased bone marrow response, red
limb blood cell production, increased viscosity and
j Asymmetrical moro’s reflex decreased blood flow leading to flushed appearance
j Associated with Erb’s palsy • Unconjugated Hyperbilirubinemia due to increased
• Xray confirms the diagnosis red cell mass
• Treatment is to immobilize the arm and shoulder • Transient Cardiomyopathy—Due to asymmetrical
using a sling for 2 weeks septal hypertrophy. May cause heart failure during
• Palpable callus within a week neonatal period. This condition is often resolved
spontaneously by 6 months of age
• Increased risk of Respiratory distress syndrome
5.5 Infant of diabetic mother
5.6 Hypothermia
• Diabetes is the most common endocrine disease
complicating pregnancy.
• Thermo- neutral range of temperature’ is the
Pathogenesis temperature range at which the basal metabolic rate
• Uncontrolled maternal hyperglycemia leads to fetal of the baby is at a minimum, oxygen utilization
hyperglycemia which in turn stimulates fetal beta is least and baby thrives well. This however varies
cells of islets of Langerhans in pancreas to secrete depending on numerous factors like gestational age.
insulin (Pederson hypothesis). Elevated insulin
• Normal axillary temperature in neonate -36.5–
levels (Hyperinsulinemia) in the fetus stimulate 37.5°C.
glycogen storage in the liver, increased lipid synthesis
• Low reading thermometer should be preferably used
and accumulation of fat. in newborn which can record temperature as low as
• Insulin being an anabolic hormone, promotes 30°C
increased growth of the fetus, especially in insulin
• Classification of hypothermia
sensitive tissues (subcutaneous fat, cardiac muscle, j Cold stress: 36–36.4°C
liver). j Moderate hypothermia: 32–35.9°C
Problems seen in fetus/Neonates j Severe hypothermia: <32°C
• Congenital malformations • Risk factors:
j Fetal heart malformations are seen in 3%–9% of j Pre-term and SGA infants (low brown adipose
diabetic pregnancies tissue, larger surface area, vulnerability to get
j Most common heart defect is transposition of exposed).
the great arteries followed by double outlet right j Cold weather
65
mebooksfree.com
• Clinical features
Normal newborn in thermal comfort typically have
j
warm and pink feet

j Cold stress is diagnosed when feet are cold but
trunk is warm. Without intervention, it often
progresses to frank hypothermia characterized by
cold feet and trunk.
j Features of hypothermia include cold skin,
acrocyanosis, sclerema, lethargy, refusal to
feeds
j Examination reveals bradycardia, tachypnea and
respiratory distress.
• Complications
j Hypoglycemia, Hypoxia and metabolic acidosis
j Disseminated intravascular coagulation—Bleeding
tendencies including pulmonary hemorrhage
• Management:
j Cold stress and Mild to Moderate hypothermia
– Immediate skin to skin contact with mother
– Radiant warmer or convection warmed
incubator
– Frequent feedings
j Severe hypothermia
– Requires incubator, thermostatically controlled
heated mattress at 37–38°C
– Fast rewarming till 34°C and then slow
rewarming. Figure 5.7 Kangaroo mother care.
– Monitor axillary temperature every half hour
till it reaches 36.5°C, then hourly for next 4 h,
2 hourly for 12 h thereafter and 3 hourly as a • Infant is kept under mother’s clothes and between
routine. her breasts
– Oxygen, empirical antibiotics and IV fluids • Mother is in semi-reclining position to avoid gastric
– Vitamin K if bleeding is present reflux in infant
– FFP, Exchange transfusion if DIC is present • Position maintained till infant no longer tolerates it;
• Prevention indicated by sweating or baby refusing to stay in KMC
j Reducing heat loss by conduction, convection and position
radiation.
B) Kangaroo nutrition
• Exclusive breastfeeding
5.7 Kangaroo mother care C) Kangaroo discharge and follow up
• Early home discharge in KMC position
Clinical Benefits
• Kangaroo mother care (KMC) refers to a specialized
care given preterm and LBW infants by placing • Infants are warm and comfortable
them in skin to skin with the mother or other • ↑Milk production in the mother
caregivers • ↑Exclusive breastfeeding rates
• Initially conceived as an alternative to conventional • ↓ the incidence of respiratory tract and nosocomial
warmer care in LBW infants; Now became a standard infections
of care in these infants • Improved weight gain
• The term ‘kangaroo care’ derived from practical • Improves thermal production in infants—Prevents
similarities to marsupial caregiving where in the cold stress and hypothermia
infant is kept warm in the maternal pouch. • Reduces the duration of hospital stay and helps in
early discharge
Components
• Physiological parameters like heart rate, respiration,
A) Kangaroo position (Fig. 5.7) oxygenation, and sleep patterns get stabilized
• Skin to skin contact between mother and infant • Improves emotional bonding between infant and
• Both mother and infant are in Vertical position mother
66
mebooksfree.com
Criteria for Eligibility Feeding:

Baby • The mother should be explained how to breastfeed
• All hemodynamically stable LBW babies while the baby is in KMC position.
• Short KMC sessions followed by longer ones as • Holding the baby near the breast stimulates milk
tolerated production.
• KMC can be provided while baby is fed via orogastric • She may express milk while the baby is still in KMC
tube, on CPAP therapy or on supplemental oxygen position.
Mother • The baby could be fed with Paladai, spoon or tube
• All mothers irrespective of age, parity, socioeconomic depending on the condition of the baby.
status Privacy
• Mothers should be clinically stable • Respect and ensure privacy of the mother and infant
• Should not have active lesions in the skin Duration
• If mother is unavailable, father or any other caretaker • Start with short sessions
can give KMC
• Gradually transition from conventional to
Initiation of KMC continuous KMC
Counseling • Mother can sleep with baby in KMC position—
• Demonstrate KMC procedure to mother reclined or semi-recumbent position about 30°
• Address any queries from horizontal
• Encourage to bring family members as their support • This can be done adjustable bed or with just pillows
is required in postdischarge home based KMC. at home.
Mother’s clothing When to stop KMC?
• Any front opening, light dress as per mother’s • KMC continued till baby finds it comfortable
cultural norms • If baby cries or fusses in KMC position, may not
• Blouse and sari or gown or night dress require KMC
Baby’s clothing • KMC is usually continued till baby attains
2500 g weight and 37 weeks
• Baby is dressed with cap, socks, nappy and front open
sleeveless shirt
KMC Procedure
KMC positioning:
5.8 Neonatal jaundice
• Baby placed between the mother’s breasts in an
upright position. • Hyperbilirubinemia is common and relatively benign
• The head should be turned to one side and in a problem in neonates during first week of life.
slightly extended position, to prevent apnea • Defined as an increased level of bilirubin in the
• This slightly extended head position keeps the airway circulation.
open and allows eye to eye contacts between the • Approximately 60% of term babies and 80% of preterm
mother and her baby. babies develop jaundice during the first week of life.
• The hips should be flexed and abducted in a ‘frog’ • Pathological jaundice is seen in 5% of babies.
position; the arms should also be flexed. • About 5—10% of them have clinically significant
• Baby’s abdomen should be at the level of the mother’s jaundice requiring phototherapy or therapeutic options
epigastrium. Physiological jaundice
• Mother’s breathing stimulates the baby thus reducing • Due to functional immaturity of the neonates to
the occurrence of apnea. handle the increased production of bilirubin due to
• Support the baby’s bottom with a sling/binder. increased enterohepatic circulation, increased fetal
• KMC positioning can also be performed in sleeping erythrocyte breakdown, decreased hepatic excretion
position and immature hepatic conjugation
Monitoring • Usually appears after 24 h and is transient in nature
• Babies should be monitored, especially during initial requiring no treatment.
stages • The total serum bilirubin increases to peak level
• Check infant’s neck position—should not be fully between 3–5 days in term infants and 5–7
flexed or extended. in preterm infants and disappears by 2nd week of life.
• Infant should breathe regularly, pink in colour and Pathological jaundice
maintain temperature • Arbitrarily defined as serum bilirubin exceeding 5 mg/
• Mother should be taught to observe these for home dL on day 1, 10 mg/dL on day 2, 15 mg/dL on day 3
based KMC and thereafter.
67
mebooksfree.com
• Appearance of jaundice within 24 h of life Breast feeding Breast milk

• Peak bilirubin greater than 15 mg/dL jaundice jaundice
• Persistence of jaundice beyond 2 weeks
Severity Mild to moderate Very high levels
(Serum bilirubin (upto 30 mg/dL)
Physiologic jaundice Pathologic jaundice
usually not more requiring exchange
Appears on second to third day Appear in first 24 h than 12 mg/dL) transfusion
of life (term) of life Treatment Increase frequency Temporary ces-
Disappears by fifth day of Variable and duration of sation of breast
life(term) breast feeding feeding
peaks at second to third day of life Variable Proper lactational (usually for 48 h)
counselling and
Peak bilirubin<13mg/dL (term), Unlimited feeding required.
<15 mg/dL(preterm)
Prognosis Self-limiting Can lead to Acute
Rate of bilirubin rise <5mg/dL/ Usually>5mg/dL/ bilirubin en-
day day cephalopathy and
Kernicterus
Breast milk jaundice
• Seen in 2%–4% of babies in 3rd–4th week of life with Causes of indirect (unconjugated) hyperbilirubinemia
bilirubin levels more than 10 mg/dL. • Physiological jaundice
• Diagnosis is made after ruling out other causes for • Breastfeeding jaundice, breast milk jaundice
prolonged jaundice. If breastfeeding is continued, • Increased production
the bilirubin gradually decreases over a period of j Blood group incompatibility (Rh, ABO, minor
3–10 weeks. blood group)
• If feeding is discontinued, bilirubin level decreases j RBC membrane defects (hereditary spherocytosis,
rapidly to the normal range within a few days. With elliptocytosis)
resumption of breastfeeding, bilirubin levels seldom j RBC enzyme defects (G6PD deficiency, pyruvate
returns to previously high levels kinase deficiency)
• Disorders of bilirubin uptake
Breast feeding jaundice j Gilbert’s syndrome
• Occurs in the 1st week of life in breastfed infants. • Disorders of conjugation
• It results due to decreased milk intake with j Crigler–Najjar Types I and II, hypothyroidism,
dehydration and/or reduced caloric intake. pyloric stenosis
• Frequent breastfeeding (>10/24 h), rooming- • Enhanced enterohepatic circulation
in with night feeding and continuing lactation j Small or large bowel obstruction or ileus
support may reduce the incidence of breastfeeding • Idiopathic
jaundice. • Others
• Breastfeeding should be continued even if they j Prematurity, sepsis, polycythemia, infant
develop breast feeding jaundice. of diabetic mother, extravascular blood
(cephalohematoma, bruising)
Breast feeding Breast milk
Causes based on time of onset
jaundice jaundice
Incidence 12-13%. 2-4%. < 24 h 24–72 h >72 h
Recurrence rate of • Rh isoim- • Physiological • Breast milk
70%. munisation jaundice jaundice
Mecha- Due to decreased UNKNOWN • ABO incom- • G6PD • UTI
nism intake of milk May be due to patibility deficiency • Sepsis
that leads to an unidentified • TORCH • Sepsis • Hypothyroid-
slower bilirubin factors (Beta infection • Extravasated ism
elimination pregnanediol) • Bacterial blood • Pyloric
and increased in breast milk sepsis • Increased stenosis
enterohepatic interfering • Congenital enterohepatic • Intestinal ob-
circulation. with bilirubin Malaria circulation struction (due
metabolism • Polycythemia to increased
Presenta- First week 7–21 days enterohepatic
tion (2–5 days) (Peak 14 days) circulation)
68
mebooksfree.com
Risk factors for significant hyperbilirubinemia • Peripheral blood smear (for RBC shape and evidence
• Primipara mother of hemolysis)
• Visible jaundice in first 24 h of life • Reticulocyte count
• Gestation < 35–36 weeks • Direct Coombs test (if mother is “O” or Rh negative)
• History of jaundice requiring treatment in previous • G6PD assay
sibling In case of sick infant with jaundice or prolonged jaun-
• ABO/Rh incompatibility dice (> 3 weeks), the following investigation are needed
• Geographic prevalence for G6PD deficiency
• Weight loss at discharge> 3% per day or > 7% • Complete blood count
cumulative weight loss • Urine examination and culture
• Evaluate for infection as indicated
Clinical evaluation
• Urine for reducing substances
• Dermal staining of bilirubin is used as a clinical • Thyroid profile (T4, TSH)
guide for assessing level of jaundice. Dermal staining • Evaluate for cholestasis (if direct bilirubin is elevated)
progress in cephalocaudal direction. The skin of
Treatment
forehead, chest, abdomen, thighs, legs, palms and
soles are examined.
• Management depends on gestation, weight, well-
being and age of the infant. Phototherapy and
Kramer’s rule: Used for clinical assessment of jaundice
exchange transfusion are treatment of choice
(Fig. 5.8a,b)
• Phototherapy remains as the mainstay in treatment
of neonatal jaundice. It consists of compact florescent
Zones Icterus upto TSB lamps in wave length range of 460 to 490 nm.
1 Face 4–6 mg% Phototherapy acts by following
2 Upper trunk 6–8 mg% j Configurational isomerization
j Structural isomerization
3 Lower trunk and thigh 8–12 mg%
j Photo oxidation
4 Arms and legs 12–14 mg% Side effects of phototherapy
5 Palms and soles > 15 mg% j Insensible water loss
j Diarrhea
Investigations j Bronze baby syndrome (when used in conjugated
The aim of investigations is to confirm the level and jaundice)
cause of jaundice and follow the response to treatment. • Double volume exchange transfusion (DVET)
The initial investigations are as follows should be done if values exceed the age specific cut
off. Indications for DVET at birth
• Total and direct bilirubin
Cord bilirubin is 5mg/dL or more
• Mother and baby blood group
j
Cord Hb is 10 g/dL or less

• Hemoglobin or packed cell volume (PCV)
j
Figure 5.8 (A) Kramer’s rule (B) Phototherapy unit.

69
mebooksfree.com
Side effects of DVET • Late Onset HDN:

j Hypoglycemia j Onset after 7 days to over weeks, usually upto
j Hypocalcemia 8 weeks.
j Hypokalemia j Unexpected intracranial bleeding
j Sepsis j Seen in infants with liver disease
• Medical management—Not used routinely Classification According To Diagnosis
Oral Phenobarbitone—Induces enzymes required
j
• Confirmed:
for bilirubin conjugation j Appropriate history of bleeding,
j Heavy metals—Inhibits hemoxygenase enzyme j Documented prothrombin time or International
and reduced hemoglobin break down. Normalized Ratio (INR) at least twice the control
value
Normal or raised platelet count,
5.9 Hemorrhagic Disease of j
No evidence of infection or disseminated

Newborn (Vitamin K deficiency
j
intravascular coagulopathy (DIC)

bleeding) • Probable:
j Appropriate history of bleeding, diagnosis other
Introduction than VKDB, unlikely but lacking full laboratory
• Vitamin K deficiency bleeding (VKDB) has replaced confirmation.
the previous term of hemorrhagic disease of Types of Bleeding
newborn. • Subcutaneous bleeding, like bruises, GI bleeding,
• Vitamin K deficiency not only occurs in newborn hematemesis, melena, nasal bleeding, hematuria,
period but continue to occur beyond neonatal period intracranial bleeding.
(late VKDB). • Warning Bleeds precede more serious bleeds.
Etiology and Pathogenesis It includes bruises, nasal bleed, umbilical oozing,
• Newborn babies are born with relatively less vitamin etc.
K reserve Investigation
• Breastfed babies are at increased risk of VKDB if • Full blood count, platelet count, prothrombin
vitamin K prophylaxis is not given time,
• Formula fed infants are at lower risk since formula • Activated Partial Thromboplastin Time (APTT),
milk is fortified with vitamin K liver function test, serum ALT, AST and serum
• Underlying latent liver disease may present with bilirubin
bleeding after 3 weeks of age. Proportion of • If facilities are available,
conjugated bilirubin, rather than total bilirubin j Serum concentration of vitamin K
estimation, is helpful at the time of bleeding or j Serum levels of undercarboxylated prothrombin
apprehending bleeding in early neonatal period metabolites, known as Protein induced in Vitamin
• Neonatal cholestasis (biliary atresia, cystic fibrosis, K absence (PIVKA-II) can also be assessed.
congenital TORCH) is more associated with VKDB.
Management
Pale stool and high color urine are suggestive of
Prophylaxis
cholestasis
• Preterm infants • All babies should receive vitamin K prophylaxis,
• Maternal risk factor: Maternal drugs affecting particularly breastfed babies. Either single IM dose or
interfering vitamin K dependent clotting factors like multiple oral doses required.
Anticonvulsant
Oral Vitamin K (Oral Phytomenadione Mixed Micellar)
j
j Rifampicin
j Isoniazid • 2 mg oral dose—three doses
j Anticoagulants • First dose at birth, second dose at 1 week, third dose
at 4–6 weeks.
Presentation
• Oral vitamin K does not prevent late VKDB, hence
• Early onset HDN: not recommended
j Onset within 24 h of birth.
j More associated with maternal ingestion of drugs Intramuscular Vitamin K (Intramuscular Phytomenadi-
affecting vitamin K metabolism like anticonvulsant. one Mixed Micellar)
• Classical HDN: • Single dose immediately after birth
j Onset 1–7 full days after birth. j If birth weight more is ≥ 1 kg, then 1 mg IM stat
j Seen in exclusively breastfed infants who have not of Vitamin K is given
received vitamin K prophylaxis. j If birth weight < 1 kg, then 0.5 mg IM stat is given.
70
mebooksfree.com
Intramuscular or Oral Vitamin K j Maternal fever (38° C)

• Intramuscular is preferable to oral vitamin K for the j Difficult or prolonged labour
following reasons: j Aspiration of meconium
j Supply and compliance with second and third Late onset sepsis:
dose of oral vitamin K may be a problem
• 72 h or more. Infections are caused by the organisms
j Intestinal absorption of oral mixed micellar thriving in the external environment of the home
K is unreliable in infants with conjugated or the hospital. The infection is often transmitted
hyperbilirubinemia (cholestatic jaundice) through the hands of the care providers
IM prophylaxis is more useful to protect who are
j
• Predisposing factors are:
sick, preterm and born to mothers taken vitamin K j LBW
antagonistic drug like anticonvulsants. j Lack of breast feeding
Threshold for treatment: j Poor cord care
• No treatment in mild case j Superficial infections (pyoderma, umbilical sepsis)
• Treatment is required if significant bleeding occurs j Aspiration of feeds
j Baby is unwell j Disruption of skin integrity with needle pricks
j Baby in first week of life in preterm baby. j Use of IV fluids
j Repeat doses may be required with significant bleeds. Pathogenesis:
• Phytomenadione vitamin K: It may have to be given • Infection in the birth canal
repeatedly
• Colonization of skin, umbilical stump, nasopharyx,
• Fresh synthesis of clotting factors occurs within 6 to 18 h conjunctiva, etc.
• In cases of life-threatening bleed—Transfusion to • Transient bacteremia
improve clotting factors immediately
• Invasion of blood stream (septicemia), leading
j Fresh frozen plasma (FFP) metastatic foci like meningitis, septic arthritis etc.
j Cryoprecipitate: If fibrinogen remains low
(<0.8 g/L) despite FFP Clinical features:
j Specific factor concentrate: If specific deficiency • Neonatal sepsis often manifests with vague and ill-
found defined symptoms and therefore, requires high index
of suspicion for early diagnosis.
• An early but non-specific manifestation is alteration
5.10 Neonatal Sepsis in the established feeding behavior. The baby, who
had been active and sucking normally, refuses to suck
and becomes lethargic or unresponsive.
Introduction: • Poor cry, Hypothermia, abdominal distension,
• When pathogenic organisms gain access into the blood vomiting and apneic spells are other common
stream, they may cause an overwhelming infection manifestations. Diarrhoea is uncommon.
without much localization (septicemia) or may get • Fast breathing, chest retractions, grunt indicate
predominantly localized to the lung (pneumonia) pneumonia.
or the meninges (meningitis). Systemic bacterial • Presence of high pitched cry, fever, seizures, blank look,
infections are known by generic term Neonatal sepsis neck retraction, bulging anterior fontanel are suggestive
which incorporates septicemia, pneumonia and meningitis. of meningitis. Shock, bleeding, sclerema and renal
Etiology: failure are indicators of overwhelming sepsis.
• Escherichia coli, staphylococcus aureus and Klebsiella Investigations:
species are predominant causes • Blood culture and other septic screening tests are sent
• Acinetobacter, Pseudomonas and Coagulase negative before starting antimicrobial therapy
Staph—Hospital acquired infections • After cleaning the skin (alcohol, povidone-iodine)
Early onset sepsis: and again alcohol, a specimen of 0.5 to 1 ml of
• Clinical symptoms appear less than 72 hrs after birth. blood can be taken in a small culture media bottle
• Infections are caused by organisms prevalent in the containing 5 to 10 ml of the liquid broth.
maternal genital tract or in the delivery area. • TLC < 5000/mm3 or >15000/mm3
• Most common presentation is Pneumonia. It can less • Absolute neutrophil count <1800/mm3
commonly presents with septicemia or meningitis. • Immature to total neutrophil ratio- more than 20%
• The predisposing factors include • CRP- more than 1mg/dL
j LBW • Micro ESR- > 15 mm/hour
j Prolonged rupture of membranes (>18 hours) • Lumbar puncture performed in all cases of late
j Foul smelling liquor onset neonatal sepsis and culture positive early
j Multiple per vaginal examinations (>3) onset sepsis.
71
mebooksfree.com
• Newer methods- PCR, DNA microarray, • Intensive care and monitoring of sick babies is
Immunoassay, IL-6,IL-8, pro-calcitonin assay required to detect complications at earliest.
Treatment: Prevention:
Supportive care:
• Provide warmth and ensure normal temperature • Hand washing, universal precautions, limit
use of devices and catheters, minimize catheter
• Start oxygen by hood or mask. If baby is cyanosed, bag manipulation, meticulous skin care, nursery design
and mask ventilation if breathing is inadequate. Instilling
and education.
normal saline drops in nostril to clear nasal block
Prognosis:
• Assess peripheral perfusion by palpating peripheral
pulses, CFT, skin colour, urine output. • Outcome depends on weight and maturity of
the infant, type of etiologic agent, its antibiotic
• If perfusion is poor, infuse NS or ringer lactate 10ml/ sensitivity pattern, adequacy of specific and
kg over 5-10 min. Repeat the same 1-2 times over the
supportive therapy
next 30-45 min/
• Dopamine and dobutamine may be required to • Early onset septicemia- high risk of adverse
outcomes
maintain normal perfusion
• In hypoglycemia, infuse 10% glucose 2ml/kg stat. • Mortality rate in neonatal sepsis- 45 to 58%
Provide maintenance fluid, electrolytes and glucose • The institution of sepsis screen for early detection
of infection, judicious and early antimicrobial
(4-6 mg/kg/min)
therapy, close monitoring of vital signs and intensive
• Add potassium to IV fluids once normal flow of urine supportive care are the most crucial factors are
has been documented
responsible for better outcome.
• Enteral feeds should be initiated early if there is no
abdominal distension and baby is hemodynamically Viral infections
stable. Feed mothers milk
• Administer vitamin K 1mg intramuscularly Time of maternal infection associated with maximum
• Transfuse packed cells, if baby has low hematocrit transmission/severity in fetus
(less than 35-40%).
CMV First trimester
• Do not use blood or plasma transfusion on routine
basis for boosting immunity. Rubella First 12 weeks (80% transmission)
Specific Care: Varicella 5 days before and 2 days after delivery
• Antimicrobial therapy constitutes the mainstay of Toxoplas- • Risk of transmission more in the last
treatment of sepsis. mosis trimester
• In a seriously sick neonate suspected of sepsis, • Severity of infection more when
appropriate antibiotics therapy should be initiated infected in First trimester
without any delay after obtaining blood samples Syphilis Mother transmits infection mostly in pri-
for culture and sepsis screen. One need not wait mary, secondary stages and only rarely in
for the results of the sepsis screen for antibiotics tertiary stage
treatment.
Intrauterine infections
Clinical situation Septicemia and Meningitis
Toxoplas- Hydrocephalus with generalized calci-
pneumonia
mosis fication / microcephaly, hepatospleno-
Community Ampicillin or Cefotaxime megaly
acquired penicillin and and gentamicin Infants treated with pyrimethamine,
Resistant strains gentamicin sulfadiazine and leucovorin.
mainly (first line) Rubella Cataract, sensorineural deafness,
Hospital acquired Ampicillin Cefotaxime Heart defects (PDA, Peripheral pulmo-
or when there is a or cloxacillin and amikacin nary artery stenosis)
low to moderate and amikacin Blue berry muffins, Thrombocytopenia,
probability of (second line) IUGR
resistant strains CMV Periventricular calcification, petechiae
Hospital acquired Cefotaxime and Cefotaxime with thrombocytopenia
sepsis or when amikacin(third and amikacin Treatment- ganciclovir/valganciclovir
there is high line) Herpes Keratoconjunctivitis, skin (5-14days),
probability of CNS (3-4 weeks), disseminated (5-7days)
resistant strains Treatment- Acyclovir
72
mebooksfree.com
Syphilis Early (birth-2years)—snuffles, macu- resulting in poorly ventilated alveoli leading to hypoxia.
lopapular rash, jaundice, periostitis, Decreased lung compliance, small tidal volumes,
osteochondritis, chorioretinitis, congeni- increased physiologic dead space, and insufficient
tal nephrosis alveolar ventilation eventually result in hypercapnia.
Late (>2 years) –Hutchinson teeth, • The combination of hypercapnia, hypoxia, and
Clutton joints, saber shins, saddle nose, acidosis causes pulmonary arterial vasoconstriction
osteochondritis, rhadges. with increased right-to left shunting through the
Treatment: Parenteral Penicillin. foramen ovale and ductus arteriosus and within the
lung itself.
Varicella Seen when delivery occurs <1week be-
fore/after maternal infection.
• Progressive epithelial and endothelial cells injury due
to atelectasis, ischemic injury and oxygen toxicity
Varicella zoster immunoglobulin—if
mother develops varicella 5 days before results in effusion of proteinaceous material into the
to 2 days after delivery. alveolar spaces (hyaline membrane disease)
< 2% of foetuses develops varicella em- Clinical features
bryopathy with infection before 20 weeks • Usually presents within the first 6 h of delivery
gestational age. • Most commonly seen in premature infants as rapid
Varicella embryopathy -Associated with and shallow respirations
limb malformation and deformation, • Tachypnea
cutaneous scars, microcephaly, chorioret- • Retractions with grunting and cyanosis
initis, cataracts, and cortical atrophy • Decreased air entry
• Downe and silverman scoring are done to objectively
quantify ‘work of breathing’
Diagnosis
5.11 Respiratory diseases • Chest x ray can confirm the diagnosis and is the
investigation of choice.
5.11.1 Respiratory Distress Syndrome • X ray: (Fig. 5.9)
j Low volume lungs
• Respiratory distress (RD) in newborn is the presence j Air bronchogram
of one or more of the following features j Reticulogranular pattern
j Respiratory rate greater than or equal to 60/min j White out lung in severe cases
j Chest retractions • Shake test done using amniotic fluid or gastric
j Grunt. aspirate—Stable foam layer at air-liquid interface
• Common in infants less than 34 weeks of gestation when mixed with ethanol suggests adequate
with overall incidence of 10- 15% and as high as 80% surfactant.
in neonates less than 28 weeks gestation Management
Risk factors • Early supportive care of premature infants
• Male gender • Treatment of acidosis, hypoxia, hypotension and
• Infants of diabetic mothers hypothermia, may lessen the severity of RDS.
• Multiple gestation
• Perinatal asphyxia
• Prematurity
• Cesarean section
Etiopathogenesis
• The basic abnormality is surfactant deficiency.
Surfactant is a lipoprotein containing
phosphatidylcholine, phosphatidylglycerol and
proteins. Surfactant production starts around
20 weeks and peaks at 35 weeks of gestation.
• Surfactant is produced by type II pneumocytes
(alveolar cells). Its function is to reduce the surface
tension of alveoli and helps to maintain alveolar
stability by preventing the collapse of small air spaces
at the end of expiration
• Deficiency of surfactant along with small respiratory
units and a compliant chest wall, produces atelectasis Figure 5.9 White out Lung in RDS.
73
mebooksfree.com
• Prevent or treat hypothermia—Infant should be placed • Phosphatidyl glycerol: can be used in IDM. Not
in incubator or radiant warmer and core temperature affected by blood or meconium contamination.
should be maintained between 36.5 and 37 °C • Lamellar body counts: Surfactant is produced from
• Respiratory distress—Requires Early Continuous lamellar bodies in type II pneumocytes. > 50000
positive airway pressure (CPAP) or ventilation lamellar bodies/microlitre indicates lung maturity.
• Provide warm humidified oxygen in order to • Surfactant to albumin ratio >55 mg surfactant/g
maintain oxygen saturation of 89 -93%. Oxygen is albumin indicates lung maturity.
given via hood, prongs, CPAP or ventilator • Foam stability index
• Mechanical ventilation and surfactant are indicated
in infants with evidence of RDS 5.11.2 Transient Tachypnea
Severe hypoxemia
of Newborn (TTNB)
j
j Poor ventilation
j Xray evidence of RDS • Also known as ‘Wet lung’
j Respiratory failure • Benign, self-limiting condition due to delayed
j Severe respiratory acidosis clearance of lung fluid immediately following birth
• Early CPAP—Most important (reduces the need for • Often seen in term/ near-term babies delivered by
ventilation) elective cesarean section
• Surfactant administration • Respiratory distress within 6hrs of birth-
j a) Prophylactic- within min of delivery usually persist for 12–24 hrs (In severe cases, upto
j b) Early rescue—within 2 h of birth 48–72 hrs)
j c) Late rescue—after 2 h of birth • Pathophysiology:
• Surfactant administration through INSURE (Intubate j Normally lungs switch from secretory to
–surfactant-extubate)/MIST (Minimally invasive absorptive mode immediately after birth.
surfactant therapy) reduces occurrence of BPD The perinatal surge in glucocorticoids and
Complications catecholamine during labour causes passive
Acute complications transport of sodium and thereby water through
• Pneumothorax and other air leaks alveolar epithelial channels, amiloride sensitive
• Patent ductus arteriosus (PDA) sodium channels and transport into interstitium
• Intracranial hemorrhage via Na-K ATPase. Absorbed fluid is cleared by
• Pulmonary hemorrhage pulmonary capillaries and lymphatics. Disruption
• Infection of this lung fluid clearance causes transient
Late complications pulmonary edema resulting in TTNB
• Retinopathy of prematurity • Risk factors
Caesarean section
•
j
Bronchopulmonary dysplasia (BPD)
Precipitous labour
•
j
Neurodevelopmental impairments
Preterm births
•
j
Other complications of prematurity
j Male gender
Prevention j Maternal diabetes
• Antenatal corticosteroids to pregnant women between j Family history of asthma
24 weeks and 34 weeks of gestation with threatened • Clinical features
preterm labor. j Babies present immediately after birth with
• A complete course consists of two doses of tachypnea, grunting and respiratory distress.
betamethasone (12 mg IM) at 24-hourly interval or j Diagnosis is made clinically by excluding other
four doses of dexamethasone (6 mg IM) at 12-hourly causes like sepsis, congenital heart disease and
intervals respiratory distress syndrome
• Antenatal steroids also reduces the incidence of • X ray features: (Fig. 5.10)
j Necrotizing enterocolitis j Hyper-expanded lungs
j Intraventricular hemorrhage j Prominent bronchovascular markings
• Antenatal steroids are contraindicated in j Fluid in minor fissure
j Maternal fever j Flattened diaphragm
j Chorioamnionitis • Treatment:
Antenatal assessment of lung maturity j This condition is mostly self-limiting.
• Lecithin: Sphingomyelin ratio: L: S ratio >2. j Requires only symptomatic measures including
However this cannot be used in IDM, transient oxygen therapy.
Erythroblastosis fetalis, asphyxia, contamination j Rarely may require short-term ventilation in severe
with blood/meconium cases.
74
mebooksfree.com
Figure 5.10 Chest xray showing hyperinflation and

Figure 5.11 Meconium Aspiration Syndrome.
bulging minor fissure (White arrow)—TTNB.
5.11.3 Meconium Aspiration • Xray features (Fig. 5.11)

Syndrome (MAS) j Overinflated lungs with flattening of diaphragm
j Bilateral non-homogenous opacities
• Approximately 13% of deliveries are complicated by j Retrosternal lucency, segmental collapse, bilateral
meconium staining of amniotic fluid (MSAF). pneumonitis
• Out of all cases with MSAF, 6% of babies aspirate j Signs of air leak—Pneumothorax,
meconium into the lungs. Pneumomediastinum.
• This either happens in utero, during delivery or • Treatment
immediately after birth. j Conservative therapy
• These babies develop hypoxemia and respiratory distress j Hypoxemia is treated with supplemental oxygen
termed as meconium aspiration syndrome (MAS). j CPAP can worsen air trapping and should be
• Pathophysiology: avoided
j Acute or chronic hypoxia j Ventilation for severe cases (High frequency and
j Passage of meconium in utero Jet ventilation)
j Gasping efforts by fetus in utero j Surfactant therapy has shown benefit in some
j Meconium aspiration. cases
• Meconium may cause partial—ball valve effect, air j ECMO can be lifesaving in refractory respiratory
trapping or complete peripheral airway obstruction- failure
atelectasis.
• Grading of severity
j Mild MAS< 40% FiO2 requirement for < 48 h 5.11.4 Apnea
j Moderate MAS> 40% for> 48 h without air leak • Cessation of respiration for > 20 seconds or less
j Severe MAS- requiring > 40% and assisted than that if associated with bradycardia and cyanosis.
ventilation • Types of apnea: Central, obstructive, mixed apnea.
• Risk factors: Post term (increasing motilin levels), • Most common type of apnea seen clinically is Mixed
IUGR, in utero hypoxia, infection type
Clinical features • Causes:
• Varying degrees of respiratory distress immediately j Immature central respiratory drive
after birth j Pneumonia, RDS,PDA,
• Meconium staining of nails, skin and umbilical cord j Intraventricular hemorrhage
• Neurological symptoms—Depressed, hypotonic with j Anemia, Sepsis
occasional hypoxic seizures j Hypoglycemia, Hypocalcemia, Hypothermia
• Complications j Apnea of prematurity
j Persistent pulmonary hypertension (PPHN) • Apnea of prematurity:
j Air leak syndromes j Occurs after 24 h of life due to immaturity of
j HIE central drive, immature chemoreceptor response
j Sepsis and inhibitory neurotransmitters.
75
mebooksfree.com
Symptoms appear within 7 days of life

j • Lumbar puncture for diagnosis of meningitis.
Diagnosis of exclusion
j • EEG to confirm seizures
• Treatment: • Imaging—Ultrasound, CT, MRI
j Proper positioning Treatment:
j Avoidance of passive neck flexion and thus • The initial steps in management are to ensure
obstruction TABC, i.e., temperature, airway, breathing and
j Treatment of the underlying cause circulation.
j CPAP / Mechanical ventilation • Correction of abnormalities like hypoglycemia and
j Drugs for apnea of prematurity: hypocalcemia with dextrose and calcium gluconate
– Methylxanthine—Caffeine if present
– Theophylline- Aminophylline • Anti-convulsant therapy: Phenobarbitone is
considered to be the drug of choice in neonatal
seizures. Dose is 20 mg/kg IV slowly over 20 min.
5.12 CNS disorders Two slow IV boluses of 10 mg/kg can be considered
if persistent seizures
5.12.1 Neonatal Seizures • Phenytoin is indicated if the maximal dosage of
phenobarbitone fails to resolve seizures or adverse
Definition: effects like respiratory depression, hypotension or
• Paroxysmal spell of altered neurologic function bradycardia are present.
• MC type- Subtle seizures (50%). Clonic, tonic and • Other drugs tried are
myoclonic are the other types. j Benzodiazepines like lorazepam and midazolam
• GTCS is not seen in neonates due to incomplete can also be used.
development of axons, dendritic process, arborisation • Pyridoxine is reserved as a last resort for refractory
and poor myelination (Only exception—Benign seizures.
familial neonatal seizures) • Prognosis:
• MC cause of neonatal seizures is cerebral hypoxia— j Seizures with worst prognosis—cerebral
Perinatal asphyxia. dysgenesis.
• MC cause of focal neonatal seizures- neonatal stroke. j In subarachnoid hemorrhage, good long term
Causes: outcome is seen.
j Best prognosis with 100% normal outcome in
• Birth asphyxia • Hyponatremia seizures due to late onset hypocalcemia.
• HIE • Inborn errors of metabolism
• Pyridoxine • Maternal withdrawal of 5.12.2 Hypoxic Ischemic
dependency medications
• Hypoglycemia • Early onset sepsis ±
Encephalopathy (HIE)
• Hypocalcemia Meningitis • Defined as insult to the fetus or newborn due to lack
• Cerebral Dysgenesis of oxygen/perfusion to various organs
• It is an important cause of permanent damage
Clinical features: to CNS tissues that may result in neonatal death
• Neonatal seizures present in decreasing order of or manifest later as cerebral palsy or developmental
frequency as delay
j Subtle Etiopathogenesis
Focal clonic
j
• Perinatal events are the most common cause of
j Multi-focal clonic HIE in absence of major congenital syndromes or
j Generalized tonic malformations.
Myoclonic
j
• The pathology of hypoxia–ischemia depends
• Seizures may manifest as eyelid blinking, fluttering or on the affected organ and the severity of
buccal-lingual movement. the injury. Early congestion, fluid leak from
• There may be peddling or autonomic movements increased capillary permeability and endothelial
because of sub-cortical neuronal discharges. cell swelling may lead to signs of coagulation
• Malformations and dysgenic states are important necrosis and cell death
causes of tonic or myoclonic types of jerks.
• These congestion are seen in pericardium, pleura,
Diagnosis: thymus, heart, adrenals, and meninges. Prolonged
• Blood glucose, Calcium, Sodium and Magnesium intrauterine hypoxia may result in inadequate
• Sepsis Screening—Hemogram, Micro ESR, CRP, Blood perfusion of the periventricular white matter leading
culture to periventricular leukomalacia
76
mebooksfree.com
• The combination of chronic fetal hypoxia and Diagnosis

acute hypoxic ischemic injury around the time • Ultrasonography is the initial preferred
of birth results in gestational age– specific investigation of choice in preterm infant and has
neuropathology limited utility in evaluation of hypoxic injury in the
term infant
Clinical features
• Diffusion-weighted MRI is the preferred imaging
• Intrauterine growth retardation and increased vascular modality in neonates with HIE as it has the increased
resistance may be first sign of fetal hypoxia sensitivity and specificity to outline the topography of
• Presence of meconium stained amniotic fluids suggest the lesion in early period
fetal distress
• Amplitude-integrated electroencephalography (aEEG)
• At birth affected infants will have may help to determine infants who are at highest risk
j Depressed or fail to breathe spontaneously for long-term brain injury
j Hypotonia
j Pallor Treatment
j Cyanosis • Whole body (systemic) or selective cerebral
j Slow heart rate therapeutic hypothermia (Neuroprotective strategy)
j Unresponsiveness to stimulus reduces mortality or major neurodevelopmental
impairment in term and near-term infants with HIE.
• CNS manifestations are more pronounced in case of
HIE. Cerebral edema develops in 24 h causing brain It is effective only if started within 6 hours after birth.
stem depression leading to seizures. Seizures can • The basic mechanism in this method is hypothermia
also occur due to hypocalcemia, hypoglycemia or decreases the rate of apoptosis and suppresses
infection production of neurotoxic mediators including
extracellular glutamate, free radicals, nitric oxide and
• Other systems manifestations are heart failure
and cardiogenic shock, persistent pulmonary lactate
hypertension, RDS, gastrointestinal perforation, • Seizures are treated with phenobarbitone at a loading
and acute kidney injury due to inadequate dose (20 mg/kg) and additional doses of 5–10 mg/
perfusion kg (up to 40 mg/kg total) may be needed. Phenytoin
(20 mg/kg loading dose) or lorazepam (0.1 mg/kg)
may be needed for refractory seizures
‘Sarnat and Sarnat’ staging of Hypoxic ischemic enceph- Prognosis
alopathy
• The outcome of HIE, which correlates with the
Signs Stage 1 Stage 2 Stage 3 timing and severity of the insult, ranges from
complete recovery to death. The prognosis varies
Level of Irritable/ Lethargic Stuporous, depending on the severity of the insult and the
consciousness Hyperalert coma
treatment
Muscle tone Normal Hypotonic Flaccid
Posture Normal Flexion Decerebrate
Tendon reflexes/ Hyperactive Hyperactive Absent 5.13 Transient metabolic
clonus disorders
Pupils Mydriasis Miosis Unequal,
poor light
reflex
5.13.1 Hypoglycemia
Seizures None Common Frequent; • Definition: Blood glucose less than 40 mg/dL in
Decerebrate general, regardless of the gestational age
posturing • Cornblath operative threshold based on risk factors
EEG findings Normal Low voltage Burst sup- j During first 24 h—45 mg/dL. Levels of 30 to
changing pression to 35 mg/dL may be acceptable once, but raised
to seizure isoelectric to if the level persists after feeding or recurs in first
activity 24 h.
Duration 24 hr–14 Days to After 24 h—45 to 50 mg/dL.
<24 h
j
days weeks j Infant with abnormal signs or symptoms —

45 mg/dL.
Outcome Good Variable Death,
j Asymptomatic infants with risk factors — 36 mg/
severe
dL.
deficits in
For any baby—<20 to 25 mg/dL requires
survivors
j
immediate therapy
77
mebooksfree.com
Physiology Treatment
• Excess glucose is stored in liver as glycogen under the • In Asymptomatic neonates
influence of insulin and released to maintain blood j Determine Babies at Risk of Hypoglycemia
sugar by j Early and frequent enteral feeding if tolerating
j Glucagon feeds
j Cortisol j Additional IV glucose maintenance if persistent
j Growth hormone hypoglycemia
j Adrenaline • Treatment in symptomatic neonates
• Neonates also utilize ketone bodies from free fatty j Immediate therapy: Bolus dose of 10% Dextrose,
acids (FFAs) as an alternate fuel for brain. 2 ml/kg (IV)
• Normal breastfed term-babies may have low normal j Maintenance therapy: Glucose infusion rate (GIR)
glucose, especially in first 24 h. Since they use ketone of 4–10 mg/kg/minute
bodies as alternate fuel, blood glucose analysis may • Target: Titrate glucose infusion to achieve stable
lead to unnecessary intervention. blood sugar values of > 40 mg/dL
Risk factors and Etiology
• Close monitoring of glucose levels (Every 15—30 min
in acute phase followed by every 4-6 h)
Reduced Hyperinsulinism: Endocrine • IV glucose is gradually tapered and switched to oral
reserve or • Infant of diabetic disease: feeding under glucose monitoring
increased mother • Pituitary: GH • In refractory hypoglycemia, not responding to IV
utilization • Hemolytic disease deficiency glucose therapy, steroids are indicated. Prednisone,
• Preterm. of newborn • Adrenal: 1-2 mg/kg/day or hydrocortisone, 5 mg/kg, every
• IUGR • Beckwith– Congenital 12 h is used
(SGA). Wiedemann adrenal • Steroids reduces peripheral glucose utilization and
• Infections syndrome hyperplasia increases gluconeogenesis.
(sepsis). • Persistent • Congenital
• Second line drugs
• Hypother- hyperinsulinemic adrenal
j Glucagon
mia. hypoglycemia hypoplasia.
j Diazoxide
• Hypoxia • Insulinoma (islet Carbohydrate
Sequelae- CNS injury:
ischemia. cell adenoma). metabolism
Fat oxidation Amino acid defect: • Predilection to involve parieto occipital cortex (MRI)
defect metabolism defect: • Glycogen and hence affect vision
Liver failure. • Tyrosinemia. storage
disease 5.13.2 Hyperglycemia
• Galactosemia.
• Plasma glucose > 145 mg/dL or blood glucose >
125 mg/dL
Clinical Features
• Causes: ELBW, sepsis, Iatrogenic (following
• Poor correlation between blood glucose levels and glucose infusion), Parenteral nutrition, neonatal
occurrence of symptoms diabetes
• Approximately 50% cases present with symptoms. • Treatment: Decrease glucose infusion rate, insulin,
• Common symptoms include irritability, poor sulfonylurea if diabetes
feeding, jitteriness, lethargy, tachycardia, tremors and
• Complication: Hyperosmolarity leading to
sweating contraction of intracellular volume and intracranial
• Severe cases can lead to apnea, cyanosis and hemorrhage
seizures.
Investigations
5.13.3 Hypocalcemia
• Blood glucose
• Electrolytes • Serum total calcium < 7 mg/dL or ionised
• Serum cortisol calcium< 4 mg/dL (1 mmol/L)
• Insulin plus c-peptide • Causes:
• Urine Ketone j Prematurity, IDM (25%–50% incidence)
• Urine reducing substance j Asphyxia
• Additional testing j IUGR
j Growth hormone assay j Vitamin D deficiency
j Thyroid hormone assay j Following exchange transfusion
j ACTH assay j Metabolic Alkalosis
j Glucagon assay j Pseudohypoparathyroidism
78
mebooksfree.com
Magnesium deficiency
j
High phosphate intake (late onset

j
hypocalcaemia)
• Symptomatic with active seizures: 200 mg/kg 10%
calcium gluconate slow intravenous infusion over
15 min under cardiac monitoring
5.14 Surgical Diseases of

Newborn
5.14.1 Congenital diaphragmatic

hernia (CDH)
• CDH occurs due to herniation of bowel loops and
liver into hemithorax through defects in diaphragm
leading on to displacement of mediastinum to the
opposite side and pulmonary hypoplasia
• Types based on location of defect
j Esophageal hiatus (hiatal)
j Paraesophageal (adjacent to the hiatus)
j Retrosternal (anterolateral Morgagni-2%–6% of Figure 5.12 Congenital Diaphragmatic Hernia.
CDH)
j Posterolateral (Bochdalek- 90% of CDH) portion
of the diaphragm
• 80-90% of the most common variety Bochdalek is in
left side. • Early antenatal diagnosis (<24 weeks)
• Associated anomalies in 30%- CNS lesions, • Lung to head ratio < 1 (<0.6–0% survival,>
esophageal atresia, omphalocoele and cardiovascular 1.35–100% survival)
lesions • Observed : Expected lung to head ratio < 25%
• Associated syndromes: • PPLV(Percent predicted lung volume) in
j Trisomy 13, 21, 18 MRI< 20%
j Brachmann de Lange syndrome • Presence of liver in thorax
j Fryns syndrome • Associated anomalies
j Pallister Killian syndrome Postnatal predictors:
j Turner syndrome • Early respiratory distress
• Clinical features: • Pulmonary hypertension
j Respiratory distress since birth or by 48 h (after a Long term outcomes: Poor catch up growth, Neurocog-
honeymoon period) nitive defects, Gastro esophageal reflux
j Scaphoid abdomen
j Mediastinal shift to opposite side
j Heart sounds are heard on right side (if lesion on 5.14.2 Necrotizing Enterocolitis (NEC)
left side)
j Bowel sounds are heard in chest • NEC is an acute inflammatory condition affecting
• CXR Fig. 5.12: Bowel loops in hemithorax. bowel of neonates
Mediastinal shift to opposite side • Most common upper GI emergency in neonates
Management Risk factors for NEC:
• Ex Utero Intrapartum (EXIT) procedure • Prematurity, enteral feeding, maternal cocaine
• Extracorporeal membrane oxygenation (ECMO)/ use
Mechanical ventilation • Babies with asphyxia, H2 blocker usage, PDA
• Surgical repair • NEC occurs in term babies also with asphyxia,
Poor prognostic factors heart disease, Polycythemia, sepsis, hypotension.
• Associated pulmonary hypoplasia • Age of onset of NEC is inversely related to gestational
• Polyhydramnios age at birth
79
mebooksfree.com
Classification: Walsh and Kliegman’s modification of Bell’s staging
Stage Systemic signs Intestinal signs Radiologic signs Treatment

Suspected NEC Temperature Abdominal distension Normal or mild ileus NPO (Nil per oral),
Stage IA instability, and occult blood in IV antibiotics for 3 days
bradycardia stool
Stage IB Same as above Gross blood in stool Same as above Same as above
Stage II A Same as above I plus absent bowel Ileus, pneumatosis NPO, IV antibiotics for
Definite NEC sounds intestinalis 7 to 10 days
Mildly ill (Fig. 5.13)
Stage II B Acidosis, Same as above Portal vein gas NPO, IV antibiotics for
Moderately ill thrombocytopenia shadows 14 days
Stage III Respiratory distress, Generalized Same + definite NPO, IV antibiotics for
Advanced metabolic acidosis, peritonitis and abscess 14 days, resuscitation,
severely ill, respiratory acidosis, tenderness inotropic support, laser
bowel intact DIC, neutropenia therapy, paracentesis
Stage III Same as above Same as above Pneumoperitoneum Same as above plus
severely ill, surgery.
Bowel perforated
Sequelae:
• Strictures, fistula,
• Short bowel syndrome, dumping syndrome
• Malabsorption, chronic diarrhea
Management
• Medical therapy (Antibiotics - Ampicillin +
Gentamicin + Clindamycin)
• Surgery - Peritoneal drainage/Bowel resection
Prevention
• Prenatal steroid therapy
• Breastmilk feeding
• Probiotics
• Avoiding aggressive enteral feeding

Figure 5.13 Pneumatosis (black arrow) seen in

Necrotising Enterocolitis.
80
mebooksfree.com
Chapter |6|
Genetics
D. Non-Mendelian disorders
6.1 Introduction a. Trinucleotide repeats
b. Mitochondrial inheritance
• The term genetics was coined by “Bateson” in 1906. c. Genomic imprinting
This branch of science deals with the study of genes d. Gonadal mosaicism
and transmission of characters from parents to
offsprings
6.3 Autosomal dominant
• Each human cell contains 46 chromosomes which
consists of 22 pairs of identical chromosomes inheritance
(autosomes) and 23rd pair of chromosome
(XY or XX) called as sex chromosomes • Involvement of one out of two homologous genes are
• Chromosomes are made up of short arm “p” and enough to manifest the disease (heterozygous state
long arm “q” and both are joined at centromere expression). Homozygotes for the dominant gene
• Genetic sex of an individual is determined by the sex often die in utero.
chromosomes • Characteristics of inheritance (Fig. 6.1)
 One X chromosome and one Y chromosome—  Affected parent can transmit the disease to 50% of
Genetic male their offspring
 Two X chromosomes—Genetic female  Males and females are equally affected and both
• A female germ cell carries X chromosome can transmit the disorder
while male germ cell carries X or Y. Combination
of these two gives rise to two possible
outcomes—XX (Genetic female) and XY
(Genetic male)
6.2 Types of genetic disorders
A. Chromosomal disorders—Any alteration in

chromosomes such as deletion, duplication or
numerical abnormalities
B. Single gene disorders/Mendelian inheritance—
Disorders caused by single gene alteration and
following Mendelian pattern of inheritance
C. Multifactorial (polygenic) disorders—involves
multiple causes including genetic and environmental
factors Figure 6.1 Autosomal Dominant Inheritance.
81
mebooksfree.com
 Unaffected parents will not transmit the disease Diseases following AR inheritance
 Can occur in successive or multiple generations
• Cystic fibrosis • Hemochromatosis
No carrier state
• Phenylketonuria • Glycogen storage diseases

 Male to male transmission is seen • Galactosemia • Sickle cell anemia

 Risk is same for all pregnancies • Homocystinuria • Thalassemias
Diseases following autosomal dominant (AD) inheritance • Lysosomal storage • Congenital adrenal
diseases hyperplasia
• Huntington disease • Familial polyposis coli
• α1-Antitrypsin • Alkaptonuria
• Neurofibromatosis • Retinoblastoma
deficiency • Friedreich ataxia
• Familial hypercholester- • Von willebrand disease
• Wilson disease • Spinal muscular atrophy
olemia • Achrondroplasia
• Myotonic dystrophy • Hereditary
• Marfan’s syndrome spherocytosis
• Polycystic kidney disease • Osteogenesis imperfecta
6.5 X-Linked recessive inheritance
• Female carriers are at the risk for having an affected

6.4 Autosomal recessive inheritance son (25%), carrier daughter (25%), and child without
mutated X-linked gene (50%)
• Involvement of both homologous genes required to • Affected males have carrier daughters and unaffected
manifest the disease (homozygous state expression) sons
• If both parents are heterozygotes, then the offsprings • Males are affected and females are carrier
would have normal phenotype (25%), heterozygotes • Characteristics of inheritance (Fig. 6.3)
(50%), and homozygotes (25%)  Both sex transmit the disease but usually
• Heterogenous state can be a carrier of the gene and trait is passed from a carrier female to male
their parents may be asymptomatic  Male to male transmission is not present
• If one parent is heterozygote and the other parent is Diseases following X-linked recessive inheritance
affected (homozygous state) then the possibility of
disease in each child increases by 50% • Hemophilia A & B • Fabry’s disease
• Recurrence risk increases by 25% for parents with a • Agammaglobulinemia • Fragile X syndrome
previous affected child • Becker’s muscular • G6PD deficiency
• Characteristics of inheritance (Fig. 6.2) dystrophy • Hunter disease
 Transmitted as horizontal pattern (occurs in only • Colour blindness • Lesch–Nyhan
one generation) • Chronic granulomatous syndrome
 Equally affects males and females disease • Lowe’s syndrome
 History of consanguineous marriage is present • Duchenne’s muscular • Wiscott Aldrich
• Almost all inborn errors of metabolism are inherited dystrophy syndrome
as autosomal recessive (AR) • Diabetes insipidus
X-Inactivation (Lyon hypothesis)

• One X chromosome in each cell is randomly
inactivated during early embryogenesis in females.
This results in equalization of X-linked gene products
in males and females.
6.6 X-Linked dominant inheritance
• Males are more commonly and severely affected and

some disorders are lethal in males
• Females are affected, but have milder phenotype
• Characteristics of inheritance (Fig. 6.4)
 Affected males transmit disease only to daughters
and sons are not affected
 Affected females transmit disease to 50%
Figure 6.2 Autosomal Recessive Inheritance. daughters and 50% sons
82
mebooksfree.com
Genetics Chapter |6|
Figure 6.3 X-Linked Recessive Inheritance.
Figure 6.4 X-Linked Dominant Inheritance.
 Daughters of affected males always inherit the • Polygenic inheritance is the expression of a
disorder phenotype, which is determined by many genes at
 No male to male transmission different loci, with each gene exerting a small additive
Diseases following X-linked dominant inheritance effect. Additive effects imply that the effects of the
• Vitamin D resistant rickets genes are cumulative and no gene is dominant or
• Incontinentia pigmenti recessive to another.
• Rett’s syndrome • Differentiation between multifactorial and polygenic
• Goltz syndrome is arbitrary as environmental and genetic factors can
be identified individually.
Conditions caused by multifactorial/polygenic inher-
6.7 Multifactorial/polygenic itance
inheritance • Neural tube defects
• Cleft lip
• Multifactorial inheritance refers to traits that are due • Cleft palate
to combination of inherited, environmental, and • Hirschsprung disease
other accidental factors. First degree relatives to the • Congenital hypertrophic pyloric stenosis
index case have similar rate of recurrence. • Diabetes mellitus
83
mebooksfree.com
6.8 Mitochondrial disorders 6.9 Genomic imprinting
• Mitochondria are only present in ovum and not in • Phenotypic expression of certain genes are
sperms. Mitochondrial DNA is exclusively derived from determined by the parent of origin
the maternal side. Mitochondrial DNA is present in the • It is selective inhibition of either a gene or set of genes
cytoplasm and any mutation within the mitochondrial coming from one of the parents
gene can lead to phenotypic defects. The inheritance of • Paternal chromosome gene inactivation—Paternal
mitochondrial gene mutations is maternal. imprinting
• Clinical manifestations of mitochondrial diseases can • Maternal chromosome gene inactivation—Maternal
be highly variable. This is because the cells contain imprinting
multiple mitochondria, which has several copies of • Examples
genome.  Prader Willi syndrome—Absence of chromosome
• Cell can have a mixture of normal and abnormal 15 of paternal origin
mitochondrial genomes, which is referred to  Angelman syndrome—Deletion of the
as heteroplasmy. Due to this varying degrees of chromosome 15 from maternal origin
heteroplasmy, a mother can be asymptomatic and yet
the children are severely affected.
• Detection of mitochondrial genome mutation can 6.10 Uniparental disomy
require sampling of the affected tissue for DNA analysis.
• Characteristics of inheritance (Fig. 6.5)
 Both sexes are affected • An offspring normally inherits one of the pair of
 All the offspring of affected female will be affected homologous chromosomes from each parent. Instead
 Daughters will transmit the disease if two copies of the same homologue from one parent
 Sons will be affected but will not transmit the is inherited, it is called uniparental disomy (UPD).
disease • Child inherits both copies of a chromosome from
same parent often due to an error in meiosis
Conditions
• Two types
• Mitochondrial encephalopathy  Uniparental isodisomy—both chromosomes or
• Lactic acidosis regions are identical
• Leigh disease  Uniparental heterodisomy—different
• Stroke-like syndrome (MELAS) chromosomes but from one parent
• Leber hereditary optic neuropathy (LHON) • Examples
• Kearns–Sayre syndrome  Beckwith Wiedemann syndrome (chromosome 11)
• Pearson syndrome  Silver Russell syndrome (chromosome 7)
• Chronic progressive external ophthalmoplegia
6.11 Down syndrome (Trisomy 21)
• Down’s syndrome is the most common chromosomal

disorder
• Occurs in 1 per 1000 live births
• The extra 21st chromosome could be either maternal
or paternal in origin
• Advanced maternal age increases the risk of Down’s
syndrome.
Cytogenetics—three mechanisms are known
A. Trisomy 21 (95% cases)—Extra copy of chromosome
21. It occurs due to nondisjunction of maternal
chromosome in meiosis stage I
B. Translocations (4% cases)—Translocation of
chromosome 21 with chromosomes 13, 14, or 15.
C. Mosaicism (1%)—the classic trisomy 21 abnormality
is only seen in some body cells while normal pattern
Figure 6.5 Mitochondrial Inheritance. seen in the remaining.
84
mebooksfree.com
Figure 6.6 (A) Facial features of Down’s syndrome. (B) Simian crease.
Clinical features • Other features include short neck with abundant

• These children have very characteristic facies neck skin, hypoplastic middle phalanx of 5th finger
resembling Mongolian race. Typical facial features (clinodactyly), characteristic single transverse palmar
include brachycephaly with flat occiput, wide open crease (Simian crease), incomplete second transverse
anterior fontanelle, flat facies with flat nasal bridge, crease (Sydney line) and increased space between first
protruding tongue, dysplastic, low set ears, upward and second toe (sandal gap) (Fig. 6.6B).
slant of eyes, and epicanthic folds (Fig. 6.6A).
Associated abnormalities
• Congenital heart disease • Malignancies

 Endocardial cushion defects Increased risk of developing lymphoproliferative

 VSD, ASD, PDA, and TOF disorders

• Gastrointestinal malformations  Acute lymphoblastic leukemia
 Duodenal atresia  Acute myeloid leukemia
 Hirschsprung disease  Myelodysplasia
• Ophthalmic problems  Transient lymphoproliferative syndrome
 Congenital cataract • Central nervous system
 Glaucoma  Hypotonia (Floppy baby syndrome)
 Nystagmus and squint  Loss of moro reflex
 Brushfield spots (small whitish iris spots)  Atlanto occipital sublaxation
• Hearing defects  Mental and growth retardation
 Conductive hearing loss (40%–60% cases)  Early onset Alzheimer’s disease
 Serous otitis media • Sexual development
• Thyroid dysfunction  Normal sexual development
 Hypothyroidism (upto 30% cases)  Females attain menarche and can be fertile
 Antithyroid antibodies are checked to rule out  Males are always infertile
autoimmune etiology  Hypospadias, cryptorchidism
• Immunity and infection • Others
 Increased risk of infection  Iron-deficiency anemia
 Pneumonia  Developmental hip dysplasia
 Respiratory tract infections are common due to CHD
Investigations  Quantitative fluorescence PCR

• Karyotyping • Radiology
• Other investigations  Only 11 pairs of ribs
 Fluorescent in situ hybridization test  2–3 ossification centers of manubrium
85
mebooksfree.com
Hypoplasia of base of skull, facial bones

 Prenatal diagnosis
Hypoplasia of middle phalanx of 5th finger
 • Fetal karyotype by chorionic villus sampling or
• Dermatoglyphics amniocentesis
 Simian crease, Sydney line • Screening with maternal serum markers (AFP levels)
 Distal palmar triradius • Triple test, Quadruple test, and PAPPA levels
 Predominance of ulnar loops on the digits and • Ultrasonography for nuchal fold thickness
radial loops on 4th and 5th fingers
Marked crease between great and second toe
6.12 Edward syndrome

(Kennedy’s crease)
Management
• Multidisciplinary management by a team of • Also known as Trisomy 18
pediatricians, geneticists, physiotherapists, • Incidence is 1 in 3000 live births
occupational therapists, and other specialties based • These babies have high mortality rate in early infancy.
on organ involvement • Approximately 50% cases die within the first week
• Early stimulation, physiotherapy, and speech therapy and >90% die within first year.
form the basis of therapy Cytogenetics
• Early stimulation is recommended for all cases and • Most cases are full trisomy 18 (95%) due to meiotic
should be started as soon as possible nondisjunction
• Screening for associated abnormalities should be • Mosaicism and translocation are rare
done and treated • Higher maternal age is a risk factor
Prognosis Clinical features
• Associated congenital heart disease is the common Head and face
cause of early mortality • Microcephaly
• Lower respiratory tract infections can be life- • Micrognathia
threatening • Cleft lip and cleft palate
• Hematological malignancies can increase mortality • Low set and malformed ears
Counseling • Occipital prominence
• Parents should be explained about the diagnosis and • Narrow nose and hypoplastic nasal alae
other associated abnormalities Trunk and extremities
• Importance of early stimulation should be • Shield-shaped chest
highlighted • Short sternum
• Risk of recurrence in future pregnancies and need for • Closed fists with index finger overlapping the 3rd digit
prenatal diagnosis and the 5th digit overlapping the 4th digit (Fig. 6.7).
Figure 6.7 (A, B) Rocker bottom foot and overlapping fingers in Edward’s syndrome.
86
mebooksfree.com
• Limited hip abduction Associated abnormalities

• Short dorsiflexed hallux Cardiac malformations
• Rocker-bottom feet • Ventricular septal defect
• Hypoplastic nails • Patent ductus arteriosus
Associated malformations • Atrial septal defect
• Cardiac malformations Renal malformations
Ventricular septal defect
 Others
 Patent ductus arteriosus • Severe developmental delay
• Renal malformations • Prenatal and postnatal growth retardation
• Gastrointestinal • Hypertonia
 Inguinal and abdominal hernia • Failure to thrive
• Others Prognosis
 Severe developmental delay • Majority of cases die within first 6 months of life
 Prenatal and postnatal growth retardation • Survivors have severe mental defects, seizures,
 Hypertonia and failure to thrive
Failure to thrive
Recurrence

Prognosis
• Risk of recurrence in subsequent pregnancies is less
• Only 5%–10% babies survive first year but have severe than 1%
mental retardation
Prenatal diagnosis
• Median survival is 3 months
• Diagnosis is possible by doing karyotyping on
Recurrence risk
chorionic villus sampling or amniotic fluid sample
• The risk is less than 1%
• In case of parent is carrier of balanced chromosomal
rearrangement, risk is high
• Most trisomy 18 fetus aborts spontaneously 6.14 Klinefelter syndrome
Prenatal diagnosis
• Second trimester screening using maternal • Most common cause of hypogonadism and infertility
biochemical markers in males
• All the three markers (unconjugated estradiol, HCG, • Most common sex chromosome aneuploidy in humans
and AFP) are classically low in maternal blood • Karyotype—47XXY
• Targeted ultrasonography • Affects 1.32 per 1000 newborns
Cytogenetics
• Extra X chromosome (47XXY)—80%
6.13 Patau syndrome • Multiple sex chromosome aneuploidies (48,XXXY;
48,XXYY; 49,XXXXY)—20%
• Mosaicism (46,XY/47,XXY)
• Trisomy 13 • Structurally abnormal X chromosomes
• Incidence is 1 in 6000 live births Clinical features
Cytogenetics • Tall and slim stature due to delayed epiphyseal
• All cases are trisomy 13 closure
Clinical features • Decreased upper segment and lower segment ratio
Head and face • Puberty is attained at normal age but testis begins to
• Scalp defects involute soon after that.
• Microcephaly and sloping of forehead • Boys develop hypogonadotropic hypogonadism
• Microphthalmia, corneal abnormalities,  Penis and testes are smaller in size
coloboma of iris  Delayed growth of pubic and facial hair
• Holoprosencephaly  Hypospadiasis, cryptorchidism, gynecomastia
• Deafness with malformed ears • Behavioral problems, impaired cognition, and
• Cleft lip/cleft palate learning difficulties
Trunk and extremities • Increased risk of breast cancer and autoimmune diseases
• Clinodactyly—overlapping of fingers and toes Diagnosis
• Polydactyly • All boys with mental retardation, children
• Hypoplastic nails with psychosocial, learning disability or school
• Hyperconvex nails adjustment problems should be screened
87
mebooksfree.com
• Karyotyping • Duplication of renal pelvis, ureter, or vessels

• ↑ Plasma estradiol, ↑ FSH, and ↓ testosterone levels • Renal aplasia or hypoplasia
Management Endocrine disturbances
• Behavioral and psychological rehabilitation • Hypothyroidism
• Testosterone replacement therapy during adolescence • Type II diabetes mellitus
period Neurological manifestations
• Learning difficulties
• Developmental delay (10%)
6.15 Turner syndrome
Skeletal
• Scoliosis
• Incidence is 1 in 5000 live births • Cubitus valgus
• Chromosome—45X Gonadal dysgenesis
• In about 75% cases, the lost chromosome is of • Infertility
paternal origin
• Primary amenorrhea
• Spontaneous abortion is most common in fetus with • Gonadoblastoma (common in mosaics)
chromosome 45X
Others
Cytogenetics
• Cataracts
• Complete or partial monosomy of X chromosome • Strabismus
(due to missing paternal X chromosome in 80% cases)
• Inflammatory bowel disease
• Mosaicism can be seen as 45,X/46,XX or 46,XY/45,X • Celiac disease
Clinical features
Investigations
• Usually they are ‘small for gestational age’ babies with • Elevated levels of Follicle stimulating hormone (FSH)
webbed neck and lymphedema of hands and feet
and luteinizing hormone (LH) are seen
during neonatal period (Fig. 6.8)
• Karyotyping
• Other dysmorphic features are short stature, • Ultrasound abdomen and pelvis shows hypoplastic
micrognathia, high arched palate, low posterior
uterus and ovaries and renal anomalies
hairline, shield chest, and widespaced nipple
• Cardiovascular evaluation for coarctation of aorta
Associated malformations
Management
Cardiac manifestations
• Height monitoring—Growth hormone therapy
• Coarctation of aorta • Hypothyroidism—Eltroxin should be started
• Bicuspid aortic valve • Ovarian hormone replacement
• Cardiac conduction defects  Conjugated estrogen at 14 years at 0.3 mg/day for
• Hypoplastic left heart syndrome 36 months
Renal manifestations  After 6 months–1 year—Cyclical therapy with
• Horse-shoe kidney progesterone is added
• Prophylactic gonadectomy in Turner syndrome
patient with Y chromosome
• Psychosocial support
Prenatal diagnosis
• Risk of recurrence—<1%
• Ultrasound
 First trimester—Increased nuchal translucency
 Second trimester—Cystic hygroma, generalized
hydrops, or increased nuchal pad
• Confirmation—karyotyping of fetal sample collected
by CVS, amniocentesis, or cordocentesis
6.16 Genetic counselling
• It is a communicative process that deals with

engagement of family members of a suspected genetic
Figure 6.8 Lymphedema Feet in Turner’s Syndrome. disorder patient. It includes
88
mebooksfree.com
 Helping family to understand the medical basis  Prenatal diagnosis and prevention
of the diagnosis, expected outcome, and currently  Therapies and referral
available management  Support groups
 Providing accurate information to families  Nondirective counseling
 Prevention of disease in future pregnancies. • Clinical situations where genetic counseling is
• Prerequisites for counseling indicated
 Taking a careful family history and constructing a
pedigree that lists the patient’s relatives (including
abortions, stillbirths, deceased persons) with their • Congenital malformations • Relatives of a person
sex, age, and state of health, up to and including • Unexplained stillbirth with chromosomal
3rd-degree relatives • Developmental delay/ translocation
mental retardation • Childhood deafness
 Gathering information from hospital records
• Neurodegenerative • Familial cancer or
about the affected person and about other family
diseases cancer-prone disease
members
• Myopathy, neuropathy, • Any familial disease
 Documenting prenatal, pregnancy, and delivery seizures, focal • Any unusual disease of
histories neurological abnormality, skin, bones, and eyes
 Reviewing the latest available literature and abnormalities of tone and • Advanced maternal
evidence about the concerned disorder power age
 Performing a careful physical examination of the • Ambiguous genitalia, • Positive screening test
affected individual (photographs, measurements) hypogonadism for a genetic disorder,
and of apparently unaffected individuals in the • Recurrent reproductive for example, Triple
family losses, infertility test, raised alpha-
 Establishing or confirming the diagnosis by the • Short stature: fetoprotein (AFP) in
diagnostic tests available proportionate or mother
 Giving the family information about support disproportionate • Prenatal diagnosis of
groups • Acutely sick infant, malformation
 Providing new information to the family as it neonate: inborn error of • Exposure to known or
becomes available metabolism (IEM) suspected teratogen
• Counselling sessions must include the following • Known genetic disease in pregnancy
 Specific condition
 Knowledge of the diagnosis of the particular
condition Online supplementary materials:
 The natural history of the condition Please visit MedEnact to access chapter wise MCQs and
 The genetic aspects of the condition and the risk of previous year pediatrics theory questions asked in various
recurrence final MBBS University examinations.
89
mebooksfree.com
Chapter |7|
Metabolic disorders
• Amino acid and organic acid metabolism disorders

7.1 Approach to a child with j Maple syrup urine disease
suspected metabolic disorder j Methylmalonic acidemia
presenting with intractable seizures j Propionic acidemia
Glutaricaciduria
and hypoglycemia (Fig. 7.1)
j
History
• Age of onset
Serum ammonia, ABG, serum lactate, and blood j Neonatal period—Galactosemia, organic
ketones estimation—Critical blood sample at the time academia
of hypoglycemia j After introduction of complementary feeds—
Acidosis+ Acidosis+ pH normal Ammonia ↑ Disorders of fructose metabolism
Ketosis+ No Ketosis Ketosis+ Acidosis+ • Consanguinity—suggests the possibility of metabolic
Lactate ↑ Lactate ↑ Lactate Ketosis+ disorder (Most IEMs are autosomal recessive)
Ammonia Ammonia normal Lactate • Timing of symptoms
normal normal Ammonia normal j Early morning after prolonged fasting usually
normal occurs in GSD, FAO
j Well after birth and symptoms after the
introduction of breast feeds usually suggest an IEM
Glycogen Fatty acid Galactosemia Amino acid • Prolongation of physiological jaundice, Escherichia
storage oxidation (nonglucose and organic coli sepsis may suggest galactosemia
disorders disorders reducing acid disor- • Symptoms suggestive of sepsis like vomiting, lethargy,
and most substances ders failure to thrive, and poor feeding often occurs in
of the car- positive in (e.g., metabolic disorders (IEM mimicks sepsis; sepsis is a
bohydrate urine) MSUD) common presentation in organic acidemias)
metabolic • History of previous recurrent abortions, early
disorders neonatal and previous sibling deaths, family history
of developmental delay and seizures strongly suggest
Differential diagnosis: the likelihood of a metabolic disorder
• Carbohydrate metabolism disorders (GSD) Examination
j Galactosemia • Doll facies can occur in Glycogen storage disorders
j Glycogen storage disorders (types 1,3,6,9) • Cataract are commonly seen in galactosemia
j Hereditary fructose intolerance • Icterus can occur in galactosemia and other IEM with
j Pyruvate carboxylase deficiency liver dysfunction
• Lipid metabolism disorders • Isolated hepatomegaly occurs in type 1 Glycogen
j Fatty acid oxidation disorders (FAO) storage disorder (Von Gierke’s disease)
j (Primary carnitine deficiency and MCAD/SCAD/ • Hepatosplenomegaly can occur in galactosemia, type
LCAD deficiency) 3, and 4 GSD
90
mebooksfree.com
Metabolic disorders Chapter |7|
Figure 7.1 Approach to suspected metabolic disorder.
• Abnormal urinary odour is an important • Liver biopsy in case of type 1 GSD may be required
examination which gives valuable clue (e.g., Burnt • Enzyme assay and genetic studies needed to confirm
sugar urine in Maple syrup urine disease) diagnosis in galactosemia
Investigations • Urinary organic acids, serum amino acids and
• Critical blood sample to be taken at the time of tandem mass spectroscopy useful to confirm organic
hypoglycemia (it includes glucose, free fatty acids, acidemias
ketones, lactate, uric acid, ammonia, insulin, cortisol, • Acyl carnitine profile ( to confirm fatty acid oxidation
growth hormone) defects)
• Serum ammonia Treatment
• Arterial blood gas for pH • Correct hypoglycemia (2 mL/kg of 10% dextrose) and
• Serum lactate perform stabilization measures.
• Blood/urinary ketones (nonketotic hypoglycemia • Treatment depends on the cause
can occur in fatty acid oxidation defects; ketotic • For galactosemia—Lactose free formula. Dietary
hypoglycemia can occur in GSD type 1 and various elimination of lactose
carbohydrate metabolic disorders) • For fructose intolerance—Dietary elimination of
• Blood counts (leucopenia and neutropenia can occur fructose containing food items
in organic academia) • For Glycogen storage disorder type 1—Uncooked
• Septic screening and blood culture to rule out sepsis corn starch to be given frequently not allowing the
• Urine for reducing substances (positive in child to fast which includes night feeds
galactosemia) • Fatty acid oxidation defect—Avoid fasting. Regular
• Urine metabolic screening periodic meals. Carnitine supplementation
• Serum triglycerides, serum uric acid elevation in type • Amino acid and organic acid disorders—Dietary
1 GSD restriction of the specific amino acid
91
mebooksfree.com
• Monitoring of growth and development is very

essential in these children
• Genetic counseling plays an important role in case of
future pregnancies
7.2 Phenylketonuria (PKU)
• Inborn error of metabolism due to the deficiency of

phenylalanine hydroxylase enzyme
• This enzyme is responsible for converting
phenylalanine to tyrosine
• Autosomal recessive inheritance
• One of the preventable causes of mental retardation
Pathophysiology
• Phenylalanine hydroxylase enzyme deficiency leads to
defective conversion of phenylalanine to tyrosine and
accumulation of phenylalanine in blood
• Excess phenylalanine in blood are metabolized by
alternate pathways and are excreted as phenyl lactic
acid, phenylacetic acid and phenylpyruvic acid in
urine (Fig. 7.2)
• The cells including neurons are deprived of
utilizing other amino acids which are needed for
their maturation and development due to elevated
phenylalanine levels
Clinical features
• Affected infants look normal at birth
• Neurological manifestations develop rapidly during
the first few months of life. It includes irritability, Figure 7.2 Phenyl alamine and tyrosine metabolism.
tremors, seizures, hypertonia, developmental delay,
low IQ and microcephaly
• Blond hair, fair skin, blue iris, skin rashes and • Serum phenylalanine should be maintained below
peculiar musty body odor 8 mg/dL in order to prevent mental retardation.
• Eczema, dental abnormalities and growth retardation
• Behavioral disorders like ADHD and autism
Diagnosis 7.3 Tyrosinemia
• Biochemical investigations aid in diagnosis
• Serum phenyl alanine levels rises within 4 hours after • Tyrosinemia is an inherited disorder of tyrosine
birth metabolism.
• On a normal diet, phenylalanine level in excess of • Tyrosine is an aminoacid used for protein synthesis
20 mg/dL on two separate occasions and is a precursor of dopamine, norepinephrine,
• Presence of abnormal urinary metabolites of epinephrine, melanin, and thyroxine
phenylalanine detected by ferric chloride test Pathophysiology
• Detection of elevated phenyl alanine and • Due to the decreased activity of the enzyme in
metabolites by Guthrie test, Fluorometric assay or tyrosine metabolism, there is elevated levels of
Tandem mass spectrometry tyrosine and methionine
• During newborn period, the diagnosis can be made • Organ damage is believed to result from
by routine screening of all neonates at 24–48 h. accumulation of metabolites of tyrosine degradation
Management • Based on enzyme deficiency, there are 3 types:
• Dietary restriction of phenyalanine and not elimination j Tyrosinemia type 1 (Hereditary tyrosinemia/
is the mainstay of treatment in phenylketonuria Hepatorenal tyrosinemia)
• Restriction should be initiated within 2 weeks of – Deficiency of fumaryl acetoacetate hydrolase
postnatal life. enzyme
92
mebooksfree.com
j Tyrosinemia type 2 (Richner–Hanhart syndrome/ skin, hair and the eyes. However, melanosomes and
Oculocutaneous tyrosinemia) melancytes are normally present
– Deficiency of tyrosine aminotransferase • Defective melanin synthesis may be generalized as in
j Tyrosinemia type 3 oculocutaneous albinism or localised to the eye as in
– Deficiency of 4-hydroxyphenylpyruvate ocular albinism
dioxygenase deficiency (4-HPPD) • Localised albinism presenting with white forelock is
Clinical features known as Piebaldism
• Jaundice and features of chronic liver disease • Associated Syndromes - Hermansky Pudlak, Chediak
• Disturbances in proximal renal tubular reabsorption higashi and Waardenburg syndromes
leading to phosphaturia, glycosuria, aminoaciduria, Clinical features
proteinuria, and rickets (Fanconi syndrome) • Depigmented and excessively fair skin which is
• Hepatosplenomegaly, Hyperinsulinism, photosensitive and does not tan
Hypoglycemia, peripheral neuropathy • White and silky hair
• Boiled cabbage odor of body fluids may be present • Pinkish or bluish iris
• Growth retardation, Vitamin D resistant rickets, • Photophobia
Hypertrophic cardiomyopathy • Normal IQ
• Ocular and skin lesions in type 2 • Refractory error and nystagmus are often present
Diagnosis Diagnosis
• Elevated levels of serum tyrosine and methionine • Diagnosis is mainly clinical
• Elevated levels of urinary and serum succinyl acetone • Molecular diagnosis is available
is diagnostic of type 1 Management
• Elevated serum alpha feto protein levels, liver • Counseling regarding wearing long sleeve
enzymes and prothrombin time clothing and use of sunscreens to protect from
• Elevated levels of methionine UV rays
• Hyperphosphaturia, hypophosphatemia, and • Ototoxic drugs must be avoided as melanin is present
generalized aminoaciduria in the cochlea
• Elevated 5-aminolevulinic acid in urine because • Regular opthalmologic follow up is essential
of succinyl acetone induced inhibition of • Genetic counseling for future pregnancies
5-aminolevulinic hydratase
• Genetic studies are available and liver biopsy is rarely
indicated
Management
7.5 Alkaptonuria
• Dietary restriction of phenylalanine, tyrosine and
methionine may result in some improvement but the • It is a rare metabolic disorder with autosomal
effect on liver function is not consistent recessive inheritance
• Nitisinone (NTBC) has a beneficial role in inhibiting Pathophysiology
tyrosine degradation • Due to the deficiency of the enzyme homogentisic
• Periodic monitoring for cirrhosis and hepatocellular acid oxidase in the liver and kidney
carcinoma • Decreased breakdown of homogentisic acid (HGA)
• Liver transplantation is the most effective therapy • HGA excreted unchanged in urine
• Accumulation of HGA leads to destruction of
connective tissue
7.4 Albinism Clinical features
• Ochronosis and arthritis are the main clinical
manifestations occurring during adulthood
• Albinism is an autosomal recessively inherited • Ochronosis is the deposition of the black pigment
disorder of the tyrosine metabolism homogentisic acid in the sclera, ear cartilage, and
Pathophysiology nose cartilage
• Arthritis commonly involves shoulder and hips.
• Degeneration and osteoarthritis like changes
occur in the spine due to the deposition of the pigment
in the articular and intervertebral disc cartilage
• Pigment deposits in the kidney can cause renal stones
• Deficiency of the enzyme tyrosinase resulting in • The only manifestation in children is the urine on
diminished or absent melanin production in the standing becomes black (Fig. 7.3)
93
mebooksfree.com
• Vitamin C administration retards ochronosis

progression and has been found useful
• Nitisinone (NTBC) inhibits the enzyme producing
HGA and has been found to have a beneficial role
• Diet less in phenylalanine and tyrosine is found
beneficial
• Symptomatic treatment for arthritis
• Genetic counseling for future pregnancies
7.6 Homocystinuria
• It is a relatively common metabolic disorder with

autosomal recessive inheritance
Pathophysiology (Fig. 7.4)
Methionine → Homocysteine -----BLOCKED------ →
Figure 7.3 Urine becoming black on standing in Cystathionine → Cysteine
Alkaptonuria. • There are 3 types. Type 1 is the most common and
classical form
Diagnosis • Type 1
• Black or greyish discoloration of the diapers or j Enzyme cystathionine synthetase in the liver is
blackening of urine on standing must suggest the deficient
diagnosis j Accumulation of homocysteine
• Benedict’s test is positive as homogentisic acid is a j Excess homocysteine gets methylated leading to
reducing substance elevated methionine level in blood
• The urine shows a black reaction with Fehling or j Plasma level of folate is low
Benedict reagent but no reaction with glucose oxidase • Type 2
• Urine organic acid testing reveals elevated levels of j Deficiency of enzyme N5-methyl THF methyl
HGA transferase
Management j This enzyme requires methyl B12 for its activity
• No specific cure is known j Methionine level in blood is low
Figure 7.4 Metabolism of Homocysteine.

94
mebooksfree.com
• Type 3 Pathophysiology
j Deficiency of the enzyme N5,10 methyl THF • Impaired activity of branched chain alpha-keto acid
reductase dehydrogenase complex is the cause of MSUD
j This enzyme is responsible for the synthesis of • Impaired activity of this enzyme complex causes
N5-THF accumulation of the metabolites of branched chain
j Methionine level in blood is low amino acids in serum, CSF and urine which may exert
Clinical features neurotoxic effects
• Levels of branched chain amino acids (leucine,
isoleucine, and valine), which are remote precursors
Type I ( Classical form) Type 2 Type 3
of the ketoacids, are also elevated
Mental retardation Dementia Develop- • The abnormal metabolites affect GABA formation in
Developmental delay Seizures mental brain and also diminishes myelin synthesis which are
Seizures Megalo- delay responsible for the neurological features
Marfanoid features blastic Seizures
Subluxation of lens anemia Mental Clinical features
Iridodonesis retardation • Affected infants are born normal
Charlie chaplin gait • Poor feeding, vomiting and lethargy appear within
Recurrent thromboem- the first week of life
bolism • Rapid progressive neurodegenerative features occur
Generalized osteoporosis • Ataxia, seizures and spasticity
• Hypoglycemic episodes may occur due to high level
of leucine in blood
Diagnosis
• Burnt sugar or maple syrup urinary odor is present
• Clinical suspicion is essential to diagnose this condition • Coma and death occur within few weeks or months
• Cyanide nitroprusside test which is a part of urine after birth if left untreated
metabolic screening detects homocysteine in urine
• Elevated levels of homocysteine and methionine are Diagnosis
diagnostic of type 1 • Urinary ferric chloride test gives navy blue color
• Elevated levels of homocysteine and low methionine • Urinary DNPH (2,4-dinitrophenylhydrazine) test
levels occur in type 2 and type 3 gives a yellow precipitate
Management
• Guthrie test is useful to pick up these cases
• Serum amino acid profile and urine organic acid
• Genetic counseling is required for future pregnancies profile reveals elevated levels of leucine, valine, and
for all the types
isoleucine
• Betaine (200–250mg/kg/day) lowers homocysteine • Neuroimaging in acute stage reveals cerebral edema
levels
in dorsal brainstem and cerebellum
• Type 1
j Restriction of methionine in the diet Management
j Large doses of pyridoxine (200–1000 mg/day) • Stabilization during acute stage and managing
found to be beneficial metabolic complications during acute stage is essential
j Folic acid (1–5 mg/day) supplementation • Treatment comprises dietary restriction of protein
improves symptoms and branched chain amino acids in diet
• Type 2 • Favorable outcome if on long term dietary
j No need to restrict methionine in the diet as it is restriction
already low • Liver transplantation improves the outcome
j Large doses of vitamin B12 should be given
• Type 3
j No need to restrict methionine in the diet as it is
already low 7.8 Galactosemia
j Folate administration improves symptoms
• Galactosemia is a metabolic disorder involving
galactose metabolism. Lactose is a disaccharide
7.7 Maple syrup urine disease sugar present in milk which consists of glucose and
galactose.
• Galactosemia is due to the deficiency of either
• Maple syrup urine disease (MSUD) is an autosomal Galactose 1—phosphate uridyltransferase or
recessive inherited metabolic disorder involving the galactokinase
branched chain aminoacids • Autosomal recessive inheritance
95
mebooksfree.com
Pathophysiology
7.9 Hereditary fructose
intolerance
• Occurs due to the deficiency of enzyme Fructose 1, 6

bisphosphate aldolase (Aldolase B)
• Infants are usually asymptomatic until exclusively
breastfed
• Symptoms are seen with ingestion of diet rich in
fructose/sucrose (table sugar, fruits, fruit juice,
sweetened cereal)
• Classical galactosemia is due to the deficiency of • Symptoms may occur early in life, soon after
galactose1-phosphate uridyltransferase birth if foods or formulas containing sugars are
• Deficiency of either enzymes results in accumulation introduced
and urinary exretion of galactose
• Causes accumulation of fructose 1 phosphate
• Alternate pathways of galactose are activated along with decrease in intracellular inorganic
• Galactose and most of its metabolites have toxic effect phosphate
on cells
• Clinical Features:
Clinical features j Asymptomatic until fructose is ingested
Classical galactosemia j Jaundice, hepatomegaly
• Children become symptomatic within a few days or j Vomiting, lethargy, irritability and convulsions
weeks after birth (after ingestion of milk) j Proximal renal tubular dysfunction
• Vomiting, diarrhea and failure to thrive are early and • Diagnosis:
common manifestations j Reducing substance in urine
• Some babies present with prolonged physiological j Assay of enzyme aldolase B
jaundice j Prolonged clotting time
• Hepatomegaly and Hypoglycemic episodes are j Hypoalbuminuria
common j Elevated bilirubin and transaminase levels
• Cataract (due to galactitol accumulation) and liver j Proximal tubular dysfunction
dysfunction appears within weeks. Can progress to • Treatment
develop cirrhosis of liver. j Complete elimination of all sources of sucrose,
• Developmental delay, pseudotumor cerebri and fructose, and sorbitol from the diet
seizures
• Mental retardation due to galactose 1—phosphate
accumulation
7.10 Approach to a child with
• Features of proximal renal tubular dysfunction can
develop glycogen storage disorder
• E. coli sepsis is common
• Hypergonadotropic hypogonadism in girls. • Glycogen storage disorder(GSD) is easily approached
Galactokinase deficiency based on the organ involved
Cataract is the only clinical manifestation. No liver or • GSD predominantly affecting liver (Hepatic/Liver
brain involvement glycogenoses)
Diagnosis
• Urinary Benedict’s test is positive (as galactose is a • Type 1 GSD (Von Gierke’s disease—Glucose-
reducing substance) 6-phopshatase deficiency)
• Newborn metabolic screening tests often pick up • Type 3 GSD (Forbe’s disease/Limit dextrinosis/Cori
these cases disease—debrancher enzyme deficiency)
• Enzyme assay—Measurement of galactose 1 • Type 4 GSD (Andersen’s disease—brancher enzyme
phosphate uridyltransferase enzyme is diagnostic deficiency)
• Genetic analysis is available even prenatally • Type 6 GSD (Her’s disease—liver phosphorylase
deficiency)
Management
• Type 7 GSD (Tauri’s disease—Phosphofructokinase
• Lactose free diet (galactose free diet) is the deficiency)
treatment of choice • Type 9 GSD (Phosphorylase kinase deficiency)
• Soy based formula useful in such cases • Type 10 GSD
• Genetic counseling for future pregnancies
96
mebooksfree.com
• GSD in which cardiac muscle is affected • Low levels of enzyme acid maltase is demonstrated
j Type 2a GSD (Pompe’s disease—lysosomal acid in leucocytes, liver, muscles and fibroblasts in type 2
maltase deficiency) GSD
• GSD with skeletal muscle involvement • Rarely muscle/skin biopsy and enzyme assay for
j Type 5 GSD (McArdle disease—muscle confirmation
phosphorylase deficiency) • Type 1 GSD—there is hypoglycemia, ketosis,
j Type 2b elevated lactate, triglycerides and uric acid.
j Type 3 Glucagon administration or galactose infusion does
j Type 7 (Tarui disease—Phosphofructo kinase not raise blood glucose.
deficiency) • Type 3 GSD—closely mimicks type 1 GSD apart from
• GSD with haemolytic anemia mild liver function derangement. Galactose infusion
j Type 7 (liver and skeletal muscle involvement is promptly causes hyperglycemia differentiating from
present) type 1
History • Type 4 GSD—Spleen may be enlarged. Ketosis is
absent. Cirrhosis can develop
• Consanguinity
• Symptoms of hypoglycemia like lethargy, irritability, Treatment
poor feeding, sweating in early morning, or while • Treatment is designed mainly to maintain
fasting normoglycemia and is achieved by continuous
• Early morning seizures or while fasting nasogastric infusion of glucose or oral uncooked
• Failure to thrive and short stature starch (uncooked starch releases glucose slowly and
• Floppiness of the limbs, fast breathing, and heart constantly)
failure symptoms in type 2 GSD • Frequent day time feeds and continuous nasogastric
• Muscle weakness, easy fatigability, exercise intolerance feeding at night is generally given
and muscle cramps in type 5 GSD • This type of feeding is needed in type 1, 3, and 4 but
• History of cola colored urine in type 7 GSD because most demanding in type 1 GSD
of hemolysis • Liver transplantation has a promising role
• History of similar features in the siblings or other • Enzyme replacement therapy is the treatment of
family members choice for type 2 GSD and has shown excellent results
Examination
• Monitoring of growth and development along with
regular immunization (especially hepatitis A and B
• Doll like facies/cherubic facies is common in type 1 vaccine) and careful usage of hepatotoxic drugs is very
GSD
essential in management these children
• Hepatomegaly in type 1,3,4,6, and other GSD where • Genetic counseling has an important role in
liver is involved
preventing recurrence in future pregnancies
• Splenomegaly in type 4 GSD
• Large tongue is seen in type 2 GSD (Pompe’s disease)
• Hypotonia and calf muscle hypertrophy in type 2 GSD
• Shifted cardiac apex and features of CCF +/− in type 7.11 Von-Gierke disease
2 GSD
• Icterus is usually absent • Von Gierke disease is type 1 Glycogen Storage
• Anemia may be present in type 7 GSD Disorder (GSD) and one of the commonly
Investigations encountered GSD clinically
• Blood glucose—Hypoglycemia Etiopathophysiology
• Blood ketones • Basic pathology is due to deficiency of enzyme
• Serum lactate glucose 6 phosphatase
• ABG to look for acidosis • The series of reactions causing release of glucose
• Lipid profile from the breakdown of glycogen and production of
• Serum uric acid glucose through gluconeogenesis is finally mediated
• ECG for prolonged PR interval and large QRS—in by the enzyme glucose-6-phosphatase which converts
type 2 GSD glucose-6-phosphate to glucose
• Chest X ray—Cardiomegaly in type 2 GSD • Because of this enzyme deficiency, glycogen is not
• Echo—Cardiomyopathy in type 2 GSD broken down to glucose and hence there is excess
• Liver biopsy for confirmation glycogen which gets accumulated in liver and there is
• Liver enzyme mildly elevated in type 4 GSD low blood glucose level
• Peripheral smear may show evidence of hemolysis in • Hypoglycemia becomes worse after overnight
type 7 GSD fasting and is attributed to the inability of liver to
97
mebooksfree.com
release glucose leading to hypoglycemia and lactic • There are seven sub-types
acidosis j Type 1MPS—Hurler syndrome—deficiency of
• Hence there is excess ketone body production along l-iduronidase
with lipolysis and free fatty acids are mobilized for – Schie—milder spectrum of hurler
energy production leading to elevated triglycerides j Type 2 MPS—Hunter syndrome—Deficiency of
and lipid levels Iduronate sulphate sulfatase
• Excess glucose 6 phosphate is shunted to HMP j Type 3 MPS—Sanfilipo syndrome—Deficiency
pathway which leads to elevated uric acid levels of Heparan-S-sulfamidase
Clinical features j Type 4 MPS—Morquio syndrome—Deficiency
• Failure to thrive of N-acetyl galactosamine 6 sulfatase
• Symptoms of hypoglycemia like lethargy, irritability, j Type 6 MPS—Morteaux lamy syndrome—
poor feeding and sweating are noted during periods Deficiency of N-acetyl galactosamine 4 sulfatase
of fasting or early morning j Type 7 MPS—Sly syndrome—Deficiency of
• Seizures commonly occur during early morning hyaluronidase
hours or following prolonged periods of fasting j Type 9 MPS—Hyaluronidase deficiency
• Doll like facies commonly termed as cherubic facies Clinical features
is noted History
• Isolated hepatomegaly is the most important clinical • Consanguineous parents—All subtypes are
sign autosomal recessive except hunter which is x-linked
Diagnosis recessive
• Clinical suspicion is essential • Vision disturbances—Children with MPS have
• Blood glucose is low corneal clouding (Fig. 7.5A). Corneal clouding is
• Blood ketones are elevated absent in Hunter and Sanfilipo syndrome. They may
• Serum lactate is elevated also have glaucoma and retinitis pigmentosa
• ABG shows acidosis • Failure to thrive—Children with MPS are short
• Lipid profile—elevated triglycerides and statured due to skeletal dysplasia
hyperlipidemia • Abdominal distension—Due to visceromegaly.
• Serum uric acid—elevated Visceromegaly is absent in Morquio
• Glucose administration improves ketosis • Subnormal intelligence. Intelligence is preserved in
• Glucagon administration does not improve glucose Schie, Morquio, Moroteaux Lamy syndromes
levels in type 1 GSD helping us to differentiate it from • Neurological—Developmental delay,
other types of GSD hydrocephalus, spinal cord compression, and
• Liver biopsy is confirmatory (liver biopsy specimen seizures
to be transported in absolute alcohol) • Musculoskeletal—Joint contractures, atlantoaxial
Treatment subluxation, carpel tunnel syndrome and scoliosis—
• Dietary therapy is the mainstay of treatment Musculoskeletal involvement is very characteristic of
• Treatment is designed mainly to maintain Morquio syndrome
normoglycemia and is achieved by continuous • Cardiac—Cardiomyopathy and valvular
nasogastric infusion of glucose or oral uncooked incompetence
starch (uncooked starch releases glucose slowly and • ENT—Progressive sensory neural hearing loss,
constantly) obstructive sleep apnea—due to large tongue and
• Frequent day time feeds and continuous nasogastric airway anomalies
feeding at night is generally given • Recurrent respiratory and ear infections
• Liver transplantation Physical examination
• Genetic counseling • General Examination—Short stature, coarse facies
(Fig. 7.5B) with large tongue, corneal clouding,
protuberant abdomen, scoliosis, and joint
contracture
7.12 Approach to
• Abdomen—Hepatosplenomegaly
muco-polysaccharidoses (MPS) • CVS—Regurgitant murmur, cardiomegaly
• CNS—Developmental delay, subnormal intelligence,
• Hereditary, progressive diseases caused by defective hypotonia, hydrocephalus, paraplegia (spinal cord
lysosomal enzymes that degrade glycosaminoglycans compression)
(GAGs) leading to intralysosomal accumulation of • Ophthalmic—Corneal clouding, retinitis pigmentosa,
GAGs. glaucoma
98
mebooksfree.com
Figure 7.5 (A) Corneal clouding. (B) Coarse facial features. (C) Short, stubby fingers. (D) Short, bullet shaped phalanges.
• Skeletal—Short, broad and stubby fingers (Fig. 7.5C), • Neuroimaging—For hydrocephalus, spinal cord
contractures, atlantoaxial instability compression
Investigations • Cervical MRI—For atlantoaxial instability
• Skeletal survey—Has to be done in any child with • Audiometry—For senorineural hearing loss
suspected MPS • Opthalmological evaluation—For corneal clouding,
j Chest X-ray shows short and wide ribs glaucoma and RP
j X-ray spine—Ovoid vertebral bodies, inferior • Behavioral and IQ testing
beaking of vertebra in Hurler, middle beaking of Management
vertebra in Morquio • Hematopoietic stem cell transplantation
j X-ray pelvis—Shallow acetabular fossa, valgus • Enzyme replacement therapy—Available for types 1,
deformity of neck of femur 2, and 6
j X-ray hand—Short, bullet shaped metacarpals • Supportive treatment
due to loss of middle constriction (Fig. 7.5D). • VP shunting for hydrocephalus
Exception—middle constriction is maintained in • Upper cervical fusion for atlantoaxial dislocation
Morquio • Laminectomy for spinal cord compression
• Urinary glycosaminoglycans are elevated in all • Corneal transplant
types. Quantitative measurement and qualitative • Glaucoma surgery
measurement of specific GAG would help in diagnosis • Hearing aids
• Tandem mass spectrometry to identify specific types • Cardiac valve replacement
• Confirmatory Diagnosis—Enzyme assay • Physiotherapy, osteotomies
• ECHO—For structural heart lesions • Behavioral therapy
99
mebooksfree.com
Characteristics of various types of MPS
Types Inheritance Defective enzyme Clinical features

Type 1—Hurler’s AR • α-l-iduronidase Severe progressive disease, mental
disease retardation, corneal
clouding, coarse facies, hepatosplenomegaly,
death usually in second decade
Type 2—Hunter’s XLR • Iduronate sulfatase Features similar to Hurler’s but with clear
disease cornea
Type 3— AR • Heparan-S-sulfamidase Slowly progressive with severe CNS
Sanfillipo’s disease • N-Acetyl-α-d- involvement. hyperactivity, behavioral
glucosaminidase problems, sleeping disorder, aggression,
• N-Acetylglucosamine- progressive dementia, mild dysmorphism,
6-sulfatase and clear corneas
Type 4— AR • N-Acetylgalactosamine- Short-trunk dwarfism, fine corneal opacities
Morquio’s disease 6-sulfatase Skeletal dysplasia
• β-Galactosidase
Type 6— AR • N-Acetylgalactosamine-4- Clouding of cornea, coarse facies,
Maroteaux Lamy sulfatase (arylsulfatase B) stiffness of joint, dysostosis multiplex,
disease hydrocephalus and valvular heart lesions
Type 7—Sly’s AR • β-Glucuronidase Fetal hydrops, mild dysmorphism;
disease hepatosplenomegaly, corneal clouding,
dysostosis multiplex
• 3 Clinical variants
7.13 Gaucher disease j Type 1 (Chronic non-neuronopathic)
– Prominent visceral involvement
– No neurological signs
• It is lysosomal storage disorder with autosomal
– Late presentation
recessive inheritance
Type2 (acute neuronopathic)
Etiopathophysiology
j
– Prominent neurological symptoms.

• Due to deficiency of tissue enzyme
– Presents in early infancy
glucocerbrosidase
– Often results in death before 2 years
• This enzyme normally splits glucose from
Type 3 (chronic neuronopathic)
glucosylceramide
j
– Both visceral and neurological features.

• Symptoms are due to accumulation of
– Presents around second year of life
glucosylceramide (cerbroside) in the
reticuloendothelial system Diagnosis
• The reticuloendothelial cells here are large with • Bone marrow examination reveals classical crumpled
eccentric nuclei with crumpled tissue paper appearance tissue paper appearance of the cytoplasm of Gaucher
of the cells due to cerebroside accumulation. These cells cells (large cerebroside laden reticuloendothelial cells
are called as Gaucher cells with eccentrically placed nuclei and crumpled silk
Clinical Features appearance cytoplasm)
• Massive firm splenomegaly. Features of • X ray thigh reveals Erlenmeyer flask deformity of the
hypersplenism may be present femur
• Liver is enlarged and marrow cavity is enlarged due • Diagnosis is confirmed by doing glucocerebrosidase
to deposits of gaucher cells enzyme assay in leucocytes or skin fibroblasts
• Expansion of the bone is prominent especially at the Treatment
lower ends of the femur and humerus. The expanded • Enzyme replacement therapy is the treatment of
lower end of femur is referred to as Erlenmyer flask choice and is highly successful and effective but
deformity expensive
• Delayed milestones, hyptonia, and seizures may be • Bone marrow transplantation is an alternative
present option
100
mebooksfree.com
• Miglustat, a substrate reducing agent is under trial • Regular neurological and vision follow up
and has shown promising results • Genetic counseling to prevent in future pregnancies
• Genetic counseling to prevent in future pregnancies
7.15 Alpha 1 antitrypsin deficiency

7.14 Abetalipoproteinemia
• Alpha 1 antitrypsin is a protease inhibitor (Pi)
• It is an inherited disorder of lipid metabolism where which is synthesized in the liver and protects lung
there is abnormality in lipoproteins alveolar tissues from destruction by neutrophil
• Lipoproteins normally transport water insoluble elastase
compounds in the serum
Etiopathogenesis
Etiopathophysiology
• PiM phenotype—over 70% of normal population
• Inherited disease characterized by the complete who have alpha 1 antitrypsin concentration ranging
absence of apolipoprotein B (apo B) containing between 0.8 to 1.8 g/L
lipoproteins from plasma
• PiZ phenotype—responsible for majority of the cases
• Possible genetic defects may be and whose concentration is usually below 0.6 g/dL
Deficient synthesis of apoprotein of beta LDL
j
• Pi null phenotype—Concentration of alpha 1
j Increased utilization of apoproteins antitrypsin level is nil
Difficulty in incorporation of apoprotein into the
j
• Deficiency of this protease inhibitor leads to
lipoprotein accumulation of alpha 1 antitrypsin in hepatocytes
• Beta lipoproteins are necessary for the formation of leading to liver injury
chylomicrons which are absent in the plasma. Hence
• Deficiency also leads to lung alveolar damage
the cholesterol and triglycerides levels are low in resulting in emphysema
this disorder
Clinical features
• Absorbed fats from the intestines cannot be transported
to plasma due to the inability to form chylomicrons • In childhood
leading to fat malabsorption in these children j Late hemorrhagic disease of infancy
Neonatal cholestasis
• Lipoproteins are responsible for the synthesis of RBC j
membrane and hence crenated thorny erythrocyte j Chronic liver disease

membrane (acanthocytosis) is observed in this • In adults
disorder j Lungs are affected leading to emphysema. They
can present as chronic cough
• Pathology in the eye and brain are also observed but
its pathogenesis is not clear j Glomerulonephritis, vasculitis, and panniculitis
are rare manifestations
Clinical features
Diagnosis
• Neurological signs such as ataxia, tremors, athetosis,
loss of vibration, and position sense • Estimation of serum alpha 1 antitrypsin levels. Low
levels are seen
• Failure to thrive, foul smelling frothy greasy bulky
stools and features of vitamin A,D,E,K deficiency due • Genetic analysis which detects mutation and which
to fat malabsorption could analyze the genotype and the phenotype
• Night blindness, visual disturbances due to retinitis Treatment
pigmentosa • Replacement therapy with intravenous alpha 1
Diagnosis antitrypsin improves serum levels but not useful in
children with chronic liver disease. However in adults,
• Peripheral smear shows characteristic acanthocytes
it is helpful in the treatment, as well as prevention of
• Fundus examination reveals features of retinitis
pigmentosa lung disease
• Stool for fat globules may be positive • Gene therapy has a promising role
• Lipid profile reveals low cholesterol and low • Liver and lung transplantation have a beneficial role
triglyceride levels in serum in the management
• Intestinal biopsy revels fat laden enterocytes
• Confirmation is by genetic studies
Treatment
7.16 Wilson disease
• Supplementation of vitamin E is essential
• Supplementation of vitamin A,D and K and dietary • Inborn error of copper metabolism
modification • Incidence is 1 in 30,000–50,000 live births
101
mebooksfree.com
• Autosomal recessive inheritance • Neuropsychiatric disturbances

Etiopathogenesis • Bony deformities with rachitic changes due to
• ATP 7B gene is defective which is mapped to proximal RTA
chromosome 13 • Hemolytic anemia
• Defective gene leads to decreased biliary excretion • Arthritis
of copper in the bile or increased binding of copper Diagnosis
to metallothionein. End result is accumulation of • Slit lamp examination : KF ring in descemet’s
copper within the cytoplasm of the hepatocytes membrane of cornea
leading to its damage. • Low serum ceruloplasmin (<20 mg/dL)
• Hepatocytes are damaged and excess copper is • High urinary copper excretion (24 hour urinary copper
released in the circulation leading to deposition of excretion more than 100 micrograms per day. It is
copper in other cells and tissues usually estimated after d-penicillamine challenge test)
• Erythrocyte damage can occur leading to hemolysis • Liver function test abnormalities can be present
• Proximal renal tubular damage can occur and this • Confirmation is by liver biopsy and quantification
may lead to fanconi syndrome of liver copper (liver copper concentration
• Copper deposition in the cornea leads to the more than 250 mg/g of dry weight of liver is
formation of Kayser Fleischer (KF) rings confirmatory)
• Copper deposition in the brain predominantly in the • Gold standard is genetic analysis for ATP 7B gene
basal ganglia leads to extrapyramidal features mutation detection
• Serum ceruloplasmin is low and it is secondary to • Screening for siblings and family members is
liver damage mandatory
• Total serum copper is low mostly as most of the Treatment
copper in serum are bound to ceruloplasmin • Treatment is life long
Clinical features • Dietary restriction of copper containing food (liver,
• The clinical presentation can be extremely varied shellfish, nuts and chocolate)
• Hepatic disease and Neurological disease are the most • Absorption of copper is prevented by treatment with
common presentation oral zinc regularly
• Hepatic disease • Already deposited copper have to be removed by
j Usually presents in younger age group. chelation therapy. d-penicillamine (10–30 mg/kg/day
j The illness can start acutely with jaundice, in 3 divided doses) chelation has to be continued for
hepatomegaly. Sometimes may progress rapidly to life
hepatic coma and death. • Ammonium tetrathiomolybdinate is useful in
j The course may often simulate chronic active chelating children with neurological manifestations
hepatitis. • Side effects of the drugs have to be monitored
j They can present with features of chronic liver periodically on follow up
disease with firm hepatomegaly and can have • Liver transplantation has a promising role in liver
features of portal hypertension and ascites. dysfunction
• Neurological disease • Screened siblings if positive but asymptomatic must
j Usually manifests in older children, in second be started on oral zinc therapy
decade of life • Hepatotoxic drugs must be avoided
j Presents with extrapyramidal features like rigidity, • Vaccination for hepatitis A, B is very important in
tremors, chorea, poor handwriting, difficulty in these children
speech, abnormal posture (dystonia) • Genetic counselling for future pregnancies
j Excessive shyness and psychiatric disturbances
Deterioration in school performance
j
j KF ring in cornea is present in all Wilson children

with neurological manifestations Please visit MedEnact to access chapter wise MCQs and
j Liver may be enlarged but jaundice is usually previous year pediatrics theory questions asked in various
absent in neurological disease final MBBS University examinations.
102
mebooksfree.com
Chapter |8|
Immunology and allergy
8.1 Classification of types of immunity
8.6 Classification of primary immunodeficiency

8.2 Immunodeficiency
B cell defects • Bruton’s agammaglobulinemia
diseases (humoral) • Common variable immunodeficiency
• Selective IgA deficiency
• Presence of one or more impaired immune defense T cell defects DiGeorge syndrome
mechanisms (cellular)
• Types Combined • Severe combined immunodeficiency
j Primary Immunodeficiency B and T cell (SCID)
diseases— defects • Ataxia telangiectasia
– Due to defective immune mechanisms in the • Wiskott Aldrich syndrome
absence of systemic disease Neutrophil Qualitative defects
– Examples: Bruton’s Agammaglobulinemia defects • Chronic granulomatous disease
DiGeorge syndrome • Myeloperoxidase deficiency
j Secondary Immunodeficiency • Chediak Higashi syndrome
diseases— Quantitative
– Due to systemic disease affecting immune • Schwachman diamond syndrome
mechanisms. Complement • Early
– Examples—HIV, protein energy malnutrition, deficiencies • Late
malignancy, drugs, etc. • Hereditary angioneurotic edema
103
mebooksfree.com
8.3 Investigations for a child with 8.4 Defects in innate immunity

suspected immunodeficiency
• Innate or natural immunity is the first defense
mechanism regardless of previous exposure
Screening tests Specific tests • It involves inflammatory cells which includes
Tests for • Immunoglobulin • B-cell enumer- polymorphonuclear white cells, dendritic cells,
B-cell (Ig) A, IgG and ation (CD19 monocytes, macrophages and NK cells
function Ig M levels or CD20)
• Antibody against • Advanced 8.4.1 Leukocyte adhesion defect (LAD)
blood group B-cell pheno-
antigens (Isohe- typing • Disorder of phagocyte function
magglutinins) • Transmitted as autosomal recessive
• Antibody titers • Three clinical types are described based on genes
to vaccines affected—LAD types 1, 2, and 3
(Antidiphtheria Pathogenesis
and antitetanus • LAD type 1—Affects Integrin β2 common chain
antibodies) (CD18) —Most common type
Tests for • Chest X-ray for • T-cell subset • LAD type 2—Affects Fucosylated proteins (Sialyl–
T-cell thymus enumeration Lewis X, CD15s)
function • Delayed skin tests (CD3, CD4, • LAD type 3—Affects Kindlin 3 and CalDAG-
(Candida, Man- CD8) GEF1protein
toux) • HLA typing
Clinical features
• Absolute lympho- • Chromosome
cyte count analysis • Neonates have delayed cord separation (beyond
• Flow cytometry for 21 days) associated with infection of cord stump
naïve T cells (CD3+ (omphalitis)
CD45RA+ cells) • Infantile period is characterized by recurrent bacterial
infections, glanzmann thrombasthenia-like bleeding
Tests for • Absolute neutrophil • Adhesion
disorder, neurological defects, and craniofacial
phago- count molecule as-
cytic cell • Respiratory burst says (CD11b/ dysmorphism
function assay CD18) • Severe gingivitis leading to loss of teeth
• Nitroblue • Mutation • Organisms causing infections include Staphylococcus
tetrazolium analysis aureus, E. coli, Candida, and Aspergillus
(NBT) dye reduc- • Enzyme as- • Signs of inflammation are absent—Absent swelling,
tion test says (G6PD, warmth, and erythema. Absence of pus formation is a
MPO, NADPH characteristic feature.
oxidase) Diagnosis
Tests for • CH50 • Component • HPE shows absent signs of inflammation and absence
comple- • C3 and C4 levels assays of neutrophils. In spite of sparse neutrophils in
ment • Activation tissues, blood examination reveals characteristic
function assays C3a, neutrophilic–leukocytosis (>250,000/mm3)
C4a, C4d, • Flow cytometry measurements of affected proteins on
C5a neutrophils (CD 15 & CD 18)
Others • Platelet count • HIV serology • Neutrophil and monocyte adherence, aggregation,
(To rule out chemotaxis, and phagocytosis are abnormal
Wiskott–Aldrich Treatment
syndrome)
• Howell–Jolly
• Early allogeneic hematopoietic stem cell
transplantation (HSCT)is the treatment of choice
bodies (To rule out
asplenia) • Prophylactic lifelong cotrimoxazole supplementation
• Erythrocyte • Small subset of LAD-2 patients respond to fucose
sedimentation rate supplementation
(rules out chronic
bacterial or fungal 8.4.2 Chediak–Higashi syndrome (CHS)
infection)
• Autosomal recessive disorder
104
mebooksfree.com
Immunology and allergy Chapter |8|
• Increased susceptibility to sepsis due to defective Management

degranulation of neutrophils (defective fusion of • No specific therapy
phagosomes and lysosomes in phagocytes) • Anti-fungal drugs for candidiasis
Pathology • Prognosis is usually good
• Mutation of LYST gene (Lysosomal traffic regulator),
located in chromosome 1q2-q44 encoding the 8.4.4 Chronic granulomatous
protein Lysomal transport protein disease (CGD)
• Oversized lysosomes and melanosomes • Group of phagocytic disorders with reduced activity
Clinical features of NADPH oxidase leading to impaired production
• Solar sensitivity, light skin and silver-colored hair of intracellular superoxide radicals. This results in
• Photophobia, rotatory nystagmus defective killing of catalase positive organisms due
• Partial oculocutaneous albinism to impaired intracellular bactericidal action.
• Neurologic deficits, progressive peripheral neuropathy Pathology
and ataxia • Phagocytic vacuoles lack microbicidal reactive
• Life-threatening Hemophagocytic lymphohistiocytosis— oxygen species and remain acidic causing impaired
Pancytopenia, fever, lymphohistiocytic infiltration of intracellular bacterial killing. Though neutrophils
viscera, and lymph nodes and monocytes are unable to kill catalase-positive
• Bleeding diathesis due to impaired platelet microorganisms, other functions like chemotaxis,
aggregation. Platelet counts are however normal phagocytosis, and degranulation are normal.
• Most common organism causing infection is S. aureus • Caused by defect involving 4 genes.
Diagnosis • X linked inheritance (>50% cases).
• Giant granular inclusion bodies in all leucocytes j CYBB gene on Chr X
• Neutropenia • Autosomal recessive inheritance
• Abnormal platelet aggregation j NCF1 gene (Chr 7), NCF2 gene (Chr 1), and CYBA
Treatment gene (Chr 16)
• Daily high dose Ascorbic acid (200 mg/day) • Rarely caused by severe G6PD deficiency
• Hematopoietic stem cell transplantation is the only • Histopathology reveals multiple granulomas in
curative therapy tissues (Pathological hallmark of CGD)
Clinical features
8.4.3 Myeloperoxidase (MPO) • Children present with recurrent infections starting
from early infancy
deficiency • Recurrent sepsis, pneumonia, lymphadenitis,
• Most common inherited disorder of phagocytes due abscesses, osteomyelitis at multiple sites
to defective oxidative metabolism • Increased risk of infection with catalase-positive
• Autosomal recessive inheritance organisms
j Staphylococcus—Most common organism in CGD
Pathology
j Pseudomonas, Enterobacteriaceae, Serratia spp.
• Azurophilic lysosomes of neutrophils and monocytes j Aspergillus, Candida
contain green heme protein known as MPO
• Infections due to Salmonella, Burkholderia cepacia, or
• Missense mutation of MPO gene is the basic pathology. Candida are commonly seen
This leads to
Impaired production of hypochlorous acid
• Hepatosplenomegaly, chronic colitis and enteritis
• Gastric outlet obstruction and ureteral obstruction
j
(HOCl) and its derivatives.

due to granuloma formation
Inability to kill Gram-positive and Gram-negative
• Restrictive lung disease, hydronephrosis, abscesses,
j
bacteria
discoid lupus
Clinical Manifestations • Family history of recurrent infections
• This condition is clinically silent. Diagnosis
• Disseminated candidiasis can occur in the setting of
diabetes mellitus.
• Flow Cytometry using dihydrorhodamine 123
(DHR) to measure oxidant production through its
• Acute myelogenous leukemia and myelodysplastic increased fluorescence when oxidized by H2O2 is the
syndromes can lead to acquired MPO deficiency.
confirmatory test
Lab diagnosis • Nitroblue tetrazolium test—No reduction in CGD
• Deficiency can be diagnosed by histochemical analysis. and positive in normal individuals
• False positive dihydrorhodamine (DHR) flow • Serology positive for Crohn disease (>80% cases)
cytometry used in the diagnosis of CGD. • Elevated ESR indicating underlying infection
105
mebooksfree.com
Treatment j Giardia
• Hematopoietic stem cell transplantation (HSCT) is j Chronic fungal infection, Pneumocystis jiroveci
the only known cure for CGD. infection
• Gene therapy tried in small group of patients • Recurrent multiple abscesses, sinusitis, pneumonia,
• Prophylaxis with daily oral Cotrimoxazole along with meningitis
Antifungal prophylaxis (Itraconazole—100 mg/day) • Small atrophic tonsils and nonpalpable lymph nodes
reduces the incidence of infections • Live polio vaccine in XLD cause paralysis and could
• Interferon-γ (IFN-γ) 50 mcg/m2 3 times a week be fatal
decreases frequency of hospital admissions • Eczema, malabsorption syndrome
• Corticosteroids are tried in antral, urethral obstruction • Neutropenia, growth hormone deficiency
and severe granulomatous colitis. Short 4–5 day Diagnosis
courses of prednisolone is given (1–2 mg/kg/day) • Serum immunoglobulins assay: decreased serum
concentrations of immunoglobulins IgG, and IgE
• Lymphoid hypoplasia (hypoplastic tonsils and
8.5 Defects in adaptive immunity lymph nodes)
• Flow cytometry demonstrates defect in circulating B
cells (CD19+) but normal circulating T cells (CD3+)
• Very specific response to foreign antigens
• Humoral immunity is mediated by circulating Treatment
immunoglobulin antibodies produced by B • Immunoglobulin replacement therapy–monthly IVIg
lymphocytes. This is the major defense against j Loading dose of 1.4 mL/kg followed by 0.7 mL/kg
bacterial infections • Daily antibiotic prophylaxis with cotrimoxazole
• Cellular immunity is mediated by T lymphocytes. Complications
This mechanism is responsible for transplant • Pneumocystis jiroveci infection
rejections and delayed hypersensitivity reactions. • Bronchiectasis
Plays a vital role in defense against viral, fungal, • Increased risk of malignancy
bacterial infections, and some tumors • Hemolytic anemia
• Rheumatoid arthritis
8.5.1 Predominant B Cell Defects
8.5.1.1 X-linked agammaglobulinemia (XLD) 8.5.1.2 Common variable immunodeficiency
(CVID)
• Also called as Bruton agammaglobulinemia,
Panhypogammaglobulinemia • Heterogeneous group of disorders characterized
• This condition is characterized by: by hypogammaglobulinemia with phenotypically
j Severe defect in B lymphocyte development normal B cells and variable defects in T cell number
j Low-levels of all three major types of and function.
immunoglobulins • j Genes involved in CVID are CDs 19, 20, 21,
j Total absence of antibody response to antigens ICOS (Inducible costimulator) and BAFF-R (B-cell
Pathology activating factor of the TNF family receptor)
• Mutated gene is in long arm of the X chromosome Clinical features
which encodes the B-cell protein tyrosine kinase • Cases present during late childhood or in adults with
(Bruton’s tk) hepatosplenomegaly
• Bruton’s tk is present in all stages of B lymphocytes and • Common presentation include recurrent ENT
plays a vital role in its development and maturation infections, granulomatous infections of lungs and
Clinical features GI tract, chronic diarrhea due to Giardia lamblia
• Affected boys are asymptomatic during the first 6 infestation and recurrent meningitis
months of life. Symptoms start after 6 months of • Increased risk of hematological malignancies
age due to decline in maternally transmitted IgG • Associated with autoimmune diseases like hemolytic
antibodies. Infants present with recurrent infections anemia, arthritis, and leukopenia
with extracellular pyogenic organisms. Diagnosis
• Common organisms causing infection are: • Levels of IgG below 2SD of normal with decreased
j Streptococcus pneumonia IgA and/or IgM levels
j Staphylococcus aureus • B cell numbers are usually normal
j Haemophilus influenza Treatment
j Mycoplasma • Intravenous immunoglobulins
j ECHO virus type 30, coxsackie virus • Antibiotic prophylaxis
106
mebooksfree.com
8.5.1.3 Hyper-IgM syndrome • Purine nucleoside phosphorylase deficiency—

presents with milder immunodeficiency beyond
• Autosomal recessive
5 years
• Due to mutations in activation-induced cytidine
deaminase (AID) gene, uracil DNA glycosylase gene • Defective descent of thymus from neck leading on to
and CD 40 gene very small thymus (<1 g)
• X linked—Mutation in CD40 ligand and NEMO • Histology reveals normal thymic epithelium but
(Nuclear factor kB essential modulator) thymocytes are reduced and corticomedullary
• Basic defect in immunoglobulin class switching and distinction is lost. Hassall corpuscles are absent.
inability to produce IgG, IgA, and IgE • Both follicular and paracortical areas of the spleen are
• Normal or High levels of IgM and low levels of IgA, depleted of lymphocytes.
IgE, and IgG • Lymph nodes, tonsils, adenoids, and Peyer patches
• Increased risk for severe pneumocystis infections and are absent or hypoplastic.
respiratory bacterial infections Clinical features
• Affected infants usually present within first few
8.5.1.4 Selective IgA deficiency months of life
• Commonest type of primary immune deficiency • Recurrent and persistent infections (recurrent or
• Characterized by defect in differentiation of naive persistent diarrhea, Pneumonia, otitis media, sepsis, and
cells to produce IgA cutaneous infections)
• Presents with recurrent respiratory infections and • Absence or hypoplastic lymphoid tissue
chronic diarrhea (Absent thymus, tonsillar tissue. No palpable
• Associated with SLE, rheumatoid arthritis, asthma, lymph nodes)
eczema, and phenytoin toxicity • Opportunistic infections with Candida albicans,
• Serum IgA levels are typically below 10 mg/dL Pneumocystis jiroveci and Viruses (CMV, EBV,
• Serum IgG and IgM levels are normal Influenza, Adenovirus, RSV, Varicella zoster, and
j Serum antibodies against IgA are seen in 44% measles virus)
cases. • Severe acquired growth failure
j Administering blood products even with traces of • Risk for severe or fatal graft-versus host disease due to
IgA can cause severe anaphylactic reactions due to inability to reject foreign tissue
IgE class antibodies against IgA. • Disseminated infections with live vaccine strains
j 5 times washed normal donor RBCs are transfused (BCG, MMR, Varicella, and Rotavirus)
to reduce the risk. Diagnosis
• Severe T cell lymphopenia can be detected on
8.5.2 Combined B cell and newborn screening using dried blood spots
T cell defects • Low absolute lymphocyte counts
• Serum immunoglobulin assay reveals low or absent
8.5.2.1 Severe combined immunodeficiency immunoglobulins (Pan-hypogammaglobulinemia)
(SCID) • Antibodies are not formed after immunization
Treatment
• Heterogeneous group of disorders characterized by
defect in adaptive immune function along with loss • This condition is a true pediatric medical
of function of B cells and NK cells. Results in most emergency.
severe form of immunodeficiency • Prevention of infections with antibiotic prophylaxis
• Both cellular and humoral immunity are affected • Frequent IVIG supplementation
• Only possibility of cure is stem cell transplantation
Pathology
• Without treatment, death invariably occurs within
• Inheritance 2 years
j Autosomal recessive—Adenosine deaminase
deficiency 8.5.2.2 Ataxia telangiectasia
j X linked—mutations of gamma chain of cytokine
receptor • Autosomal recessive with mutation in ATM gene
located on chromosome 11q 22–23
Types
• Complex syndrome with immunologic,
• MC type is X-linked SCID (X-SCD) due to mutation in neurologic, endocrinologic, hepatic, and cutaneous
Common Cytokine Receptor γ Chain (γC)
abnormalities
• Second most common form of SCID is absence of the • Excessive chromosomal breakage and increased
enzyme adenosine deaminase (ADA) (15% patients) sensitivity to ionizing radiation
107
mebooksfree.com
Clinical features • Monthly infusions of intravenous immunoglobulin

• Progressive cerebellar ataxia manifests when child (IVIG) is treatment of choice
starts to walk. Progressive worsening and most cases • Bone marrow or cord blood transplantation is curative
are wheel chair bound by 10–12 years
• Oculocutaneous telangiectasia—Develops by
3–6 years involving bulbar conjunctiva 8.5.2.4 Hyper IgE syndrome (Job syndrome)
• Chronic sinopulmonary disease (sinusitis, tonsillitis, • Autosomal dominant—Mutation in STAT3 gene
pneumonia) • Characterized by:
• Increased risk of lymphoreticular malignancy j Recurrent skin and respiratory infections
• Humoral and cellular immunodeficiency j Chronic eczematous dermatitis
j Isolated absence of IgA j Skeletal or bony abnormalities
Diagnosis • Recurrent infection with Staphylococcus aureus is
• Presence of acanthocytes in the peripheral smear characteristic. Other organisms include Candida albicans
• Serum IgA, IgG2 subclass and IgE levels are usually • Elevated eosinophil count and
reduced • Elevated serum levels of IgE (>2000 IU/mL)
• Hypoplastic thymus with absent Hassall’s corpuscles
• Reduced CD3, CD4 T cells and elevated or normal 8.5.3 Predominant T cell defects
CD 8 T cells.
8.5.3.1 DiGeorge syndrome
8.5.2.3 Wiskott–Aldrich syndrome
• This disorder arises due to dysmorphogenesis of the 3rd
• X linked recessive disease and 4th pharyngeal pouches during embryonic period
• Mutation at Xp 11.22–11.23 in gene encoding WAS • Hypoplasia/aplasia of the thymus and parathyroid
protein present in cytoplasm of lymphocytes and glands
platelets Pathology
• Characterized by the triad of: • Microdeletion of specific DNA sequences from
j Eczema chromosome 22q11
j Thrombocytopenia • Associated with:
j Recurrent serious bacterial infections j CATCH 22 syndrome (cardiac, abnormal facies,
• Severe IgM deficiency thymic hypoplasia, cleft palate, hypocalcemia)
• Defective T cell signaling due to deficient CD43 in j CHARGE syndrome (coloboma, heart defect,
lymphocytes. choanal atresia, growth, or developmental
Clinical features retardation, genital hypoplasia, and ear anomalies
• Atopic dermatitis (eczema) manifests in first year including deafness).
of life Clinical features
• Prolonged bleeding tendencies especially episodes of • Characteristic facies (hyperteleorism, antimongoloid
bloody diarrhea in infancy or following circumcision slant, low set ears, hypoplastic mandible, dysplastic
• Impaired humoral antibody response to ears, short philtrum and bifid uvula)
polysaachaaride antigens leads to recurrent and • Complete aplasia of thymus resembling SCID Thymic
severe infections with Streptococcus pneumoniae, hypoplasia predisposes to infections with low-grade
Hemophilus influenza, Neisseria meningitides, and or opportunistic pathogens—fungi, viruses, and
Pneumocystis jiroveci Pneumocystis jiroveci
• Increased risk of lymphoreticular malignancies • Hypocalcemic tetany can be the presenting feature in
associated with EBV neonatal period
• Thrombocytopenic purpura • Affected children have normal growth
• Absent antibody response to polysaccharide vaccines • Associated with Congenital heart defects like coarctation
Diagnosis of aorta, right sided aortic arch, ASD, and VSD
• Thrombocytopenia with small sized platelets • Associated with Esophageal atresia
(Microplatelets). Mean platelet volume is typically Diagnosis
less than 6 fL • Absent thymus on chest X-ray
• Low serum level of IgM • Hypocalcemia
• Elevated IgA and IgE • Low number of T cells and impaired T-cell function
• Normal or slightly low IgG concentration • Immunoglobulin (Ig) A may be diminished, IgE will
Treatment be elevated and other immunoglobulins levels are in
• Adequate nutrition, vaccination with killed vaccines normal range
108
mebooksfree.com
Treatment Risk factors

• High dose IV calcium and vitamin D • Atopy
• Thymic transplantation • Positive family history of atopy
• Spontaneous resolution in some cases • Elevated serum immunoglobulin IgE
• Hematopoietic stem cell transplantation in severe Pathogenesis
T cell defects • Allergen exposure in a host with atopy results in
specific IgE production
• Early phase allergic response—Appears immediately
8.6 Intravenous immunoglobulin after allergen exposure. Allergen causes bridging
of IgE to mast cells—>Mast cell degranulation—
>Release of inflammatory mediators (histamine,
• Pooled normal polyspecific IgG derived from the leukotrienes and prostaglandins)
plasma of healthy, screened donors. Each IVIG batch
represents a pool of 4000–8000 donors
• Late phase allergic response: Occurs 4–8 h
following allergen exposure. Inflammatory
• Most IVIG preparations contain 90% monomeric IgG
cells (eosinophils, basophils, mast cells, and
with only small amounts of IgA and IgM.
mononuclear cells) infiltrate nasal mucosa. These
• Mechanism of action:
cells release proinflammatory mediators (IL-3, IL-
j Actions mediated via the variable regions of Fab
5, IL-13, etc.) which further sustain inflammation.
Actions of Fc region on a range of receptors
• Secondary exposures with allergen causes more
j
j Actions mediated by complement binding on

severe response even with minimal allergen
Fc fragment
• Dose Clinical features
j Single infusion of 2 g/kg • Intermittent nasal congestion, itching, rhinorrhea,
j Replacement therapy with dose is 0.4–0.6 g/kg sneezing, and conjuctival congestion. Symptoms are
every 3–4 weeks often seen immediately after exposure to allergen
• Definite indications especially in the morning.
j Hypogammaglobulinemia • Associated features include headache, anosmia, nasal
j Kawasaki disease block, and disturbed sleep.
j Guillian barre syndrome • Often misdiagnosed as upper respiratory infection.
j Idiopathic thrombocytopenic purpura • Allergic salute—Upward rubbing of nose with palm.
j Neonatal sepsis This results in characteristic horizontal skin crease
j Neonatal jaundice over the nose.
• Other indications • Allergic gape—Open mouth breathing due to nasal
j Myasthenia gravis obstruction
j Autoimmune neutropenia • Allergic shiners—Dark circles under eyes
j Neonatal alloimmune • Other features include open mouth breathing and
j Autoimmune thrombocytopenia dental malocclusion.
j Lupus crisis • Classification
j Dermatomyositis
• Adverse effects Type Features
j Allergic reactions, including anaphylaxis Mild intermittent Symptoms for <4 days per week
j Chills or rigors or <4 weeks at a time
j Risks bloodborne transmission like hepatitis C And
infection Normal sleep, daily activities
j Acute renal failure Moderate to severe Symptoms for <4 days per week
intermittent or <4 weeks at a time
And
Allergic diseases Impaired sleep and daily activities
Mild persistent Symptoms for >4 days per week
or >4 weeks at a time
And
8.7 Allergic rhinitis Normal sleep, daily activities
Moderate to severe Symptoms for >4 days per week
• Chronic inflammatory disease of nasal mucosa persistent or >4 weeks at a time
• Characterized by nasal congestion, irritation, And
rhinorrhea, and bouts of sneezing Impaired sleep and daily activities
109
mebooksfree.com
Lab diagnosis j Chest tightness

• Allergy skin tests j Change in voice
• Serum immunoassay for allergen specific IgE • GIT
• Eosinophils in nasal smear j Dysphagia
• Peripheral eosinophilia j Abdominal pain
• Elevated total serum IgE levels (>100 IU/ml) j Vomiting
Management • CVS
• Basic principles of treatment are to provide j Hypotension
relief from symptoms and to prevent j Weak thready pulse, shock
exacerbations • CNS
• Avoiding allergen exposure j Headache
• First line drugs—Reduces allergic symptoms and j Unresponsiveness
induces remission j Hypotonia
j Oral antihistaminics—Cetrizine, j Seizures
loratidine Diagnosis
j Inhaled corticosteroids—Beclomethasone, • Clinical history and findings
flunisolide, triamcinolone, mometasone, • Serum Histamine and tryptase levels
fluticasone, and budesonide • C1 inhibitor functional assay (C1INH) (hereditary
• Adjunctive treatment angioneurotic edema)
j Anticholinergic ipratropium bromide • Urine vanillylmandelic acid (VMA) and serum
nasal spray serotonin levels (carcinoid syndrome)
j Intranasal decongestants (phenylephrine • Radioallergosorbent test (RAST)
and oxymetazoline) Treatment
j Leukotriene Antagonist—montelukast • Temperature, airway, breathing, and circulation
j Allergen immunotherapy • Early and prompt administration of epinephrine
j Omalizumab (anti-IgE antibody) • Epinephrine (0.01 mg/kg/dose) intramuscular in
lateral thigh
• H1 and H2 blockers
8.8 Systemic anaphylaxis • Short course of oral steroids
• Severest type of allergic reaction

• Rapid in onset and life threatening 8.9 Bronchial asthma
• Characterized by
j Vascular shock
Definition
Widespread edema
• Chronic inflammatory airway disease, resulting in
j
j Respiratory distress
episodic airflow obstruction
• Systemic anaphylaxis is a classic example of Type 1 • Common chronic disease of childhood and the
hypersensitivity reaction
leading cause of childhood morbidity
• It occurs in sensitized individuals in hospital • More than 80% cases present within 5 years of age
settings after administration of foreign proteins (e.g.,
antisera), enzymes, hormones, polysaccharides, and
• Basic pathological features include
j Airway inflammation
drugs (e.g., penicillin)
j Airway obstruction mainly due to bronchospasm,
• In the community setting following exposure to food associated with mucosal edema and stagnation of
allergens (e.g., peanuts, shellfish), and insect toxins
the mucus
(e.g., bee venom)
j Airway hyperreactivity to aerobiologicals and irritants
Clinical features j Airway remodeling in uncontrolled asthma
• General Etiology
j Flushing, weakness
j Anxiety, apprehension • Inherent biological and genetic susceptibility along
• Skin/mucous membranes with environmental factors play a major role
j Urticarial lesions Host factors
j Itching in lips, tongue, oral cavity • Genetic
j Swelling and difficulty in swallowing j More than 100 genetic loci have been linked to atopy
• Respiratory j Most commonly associated are proallergic and
j Hoarseness proinflammatory genes
110
mebooksfree.com
Epigenetic modification is an important factor in

j j Angiogenesis
the transmission of asthma j Smooth muscle hypertrophy and hyperplasia
• Obesity
• Sex—male preponderance
• Infections—predominantly viral infections caused
by RSV, adenovirus, rhinovirus, influenza virus,
parainfluenza virus, etc.
Environmental
• Allergens
j Indoor—MC is dust mite followed by domestic
mites, furred animals (dogs, cats, mice), cockroach
allergens, fungi, molds, yeasts.
j Outdoor—Pollens, fungi, molds, yeasts.
• Season
j Higher incidence is seen in monsoon climate Pathophysiology of bronchial asthma exacerbations
followed by winter. Acute attacks are less common Clinical features
in summer • Recurrent cough—The cough is dry, intermittent,
• Tobacco smoke—Children are most common victims more at night, or early morning time; often induced
of passive smoking by physical or emotional stress.
• Indoor/outdoor air pollution • Episodes of cough, wheeze, and chest retractions.
j Nitrogen oxide, ozone, and SO2 • Chest tightness, chest pain, post-tussive vomiting
• Food allergies— • Abdominal pain rarely occurs due to overworking of
j Common with grapes, banana, guavas, citrus fruits, expiratory abdominal muscles
and ice creams • Though afebrile wheezing is classical of bronchial
• Pets asthma, superimposed viral infection and fever is also
j Saliva, urine, and dander of pets like cats and seen commonly
dogs • Recurrent episodes are exacerbation of symptoms
Pathophysiology • Personal atopy, family history of atopy or asthma
• Initiated in response to sensitization to allergen. As • History of specific triggers
the allergen enters the epithelial cell it encounters • Seasonal exacerbations
dendritic cells and gets broke down into small pieces • Prompt Relief with bronchodilators
(epitomes) • Presence of comorbid factors like allergic rhinitis,
• B lymphocytes produce interleukins, IL-4 and IL-13 sinusitis, eczema, and conjunctivitis
which stimulates production of IgE antibodies. Mast • Clinical variants of bronchial asthma
cell binds to large number of IgE molecules of various j Exercise induced asthma
allergens j Nocturnal asthma
• Activation of mast cells releases histamine and Diagnosis
continued exposure to allergen brings eosinophils
into action. The eosinophilic granules release • Diagnosis of asthma is mainly by history and physical
examination
toxic chemicals such as eosinophil cation protein,
eosinophil derived neurotoxin and major basic Preschool children
protein, which damage the epithelium and sensory • Infant who has more than 3 episodes of wheeze
nerves causing hyperresponsiveness to nonallergic in 1 year with family history of asthma, has atopic
stimuli features, afebrile episodes and cough persisting more
• The mediators released due to allergic reaction than 2 weeks with good response to bronchodilators.
act on the cells of the airway leading to smooth School-going children
muscle contraction, mucus hypersecretion, plasma • Spirometry
leakage, edema, activation of cholinergic reflexes j Normal values for children available on the basis
and activation of sensory nerves, which leads to of height, gender, and ethnicity
amplification of the continuing inflammatory j Monitoring Asthma and efficacy of treatment
response j Measures FVC, FEV 1, and FEV 1/FVC ratio
• Chronic inflammation leads to following structural j Lung function abnormalities in asthma
changes – Obstructive disease
j Mucus cell hyperplasia - Low FEV1
j Subepithelial fibrosis - FEV1:FVC ratio <0.80
111
mebooksfree.com
– Bronchodilator response (to inhaled β-agonist) • Skin testing with allergens is the gold standard
- Improvement in FEV1 ≥12% and ≥200 mL to identify the specific allergens and used before
– Exercise challenge immunotherapy for aeroallergens
- Worsening in FEV1 ≥15% • Bronchial provocation/challenge tests are of no use
– Daily peak flow or FEV1 monitoring: day to day and should be avoided
and/or A.M.-to-P.M. variation ≥20% Differential diagnosis—All children with wheezing are
– Peak expiratory flow rate: not asthmatic
- >15% increase in PEFR after inhaled short
• Foreign body aspiration
acting β2 agonist
• Wheeze associated lower respiratory tract infection
- >15% decrease in PEFR after exercise
• Chronic rhinosinusitis
- Diurnal variation >10% in children not on
• Gastro-esophageal reflex disease
bronchodilator
• Vocal cord dysfunction
• Eosinophil count - Increased count in the blood is • Hypersensitivity pneumonitis
suggestive of an allergic reaction
• Pulmonary parasitic infections
• Elevated total and specific IgE levels • Pulmonary tuberculosis
• Chest X-ray is not needed to diagnose asthma. It is • Asthma masquerading conditions
needed only when the diagnosis is not clear or any j Bronchiolitis obliterance
complications are suspected j Primary ciliary dyskinesia
j Often normal j Congestive cardiac failure
j Bilateral hyperinflation and prominent j Interstitial lung disease
bronchovascular markings j Mass lesions compressing—larynx, trachea,
j Helpful in identifying masqueraders bronchi
Classification based on asthma severity
Moderate Severe
Intermittent Mild persistent Persistent persistent
Daytime symptoms ≤2 days/week >2 days/week but not Daily Throughout the
daily day
Night-time awakenings ≤2×/month 3-4×/mo >1×/week Often daily
In ≥5 years
Use of Rescue therapy ≤2 days/week >2 days/week and not Daily Several times
(Short acting β agonist) more than 1× on any per day
day
Interference with normal None Minor limitation Some limitation Extreme
activity limitation
FEV1 percent predicted >80% predicted ≥80% predicted 60%–80% predicted <60% predicted
FEV1:FVC ratio >85% >80% 75%–80% <75%
Age 5–11 years
Treatment j Dust mites, cockroach, fungus, and pets

The management of asthma includes the following j Avoid strong odors, smoke, mosquito coil burning,
• Education and especially tobacco smoke
• Environment control j Have indoor plants to absorb formaldehyde and
• Pharmacotherapy volatile organic compounds from modern furniture
• Regular follow-up Pharmacotherapy
Education • The drugs used in the treatment of asthma includes
quick relievers, preventers and long-term symptoms
• Parents should be educated and misconceptions relievers
about the disease, noncommunicability of the
• Relievers—Medications to be used on as-needed basis
disease, fear of inhalers and steroids should be cleared to relieve symptoms quickly
Environment control j Short acting beta agonist—Salbutamol
• It is the most important factor in the control of asthma. j Anticholinergic agent—Ipratropium bromide,
The aim should be to avoid allergens and irritants always used in combination with salbutamol
112
mebooksfree.com
• Controllers—Medications to be taken on daily long – Leukotriene synthesis inhibitor—Zileuton

term basis (Not approved for children <12 years)
j Inhaled corticosteroids—Budesonide, fluticasone, j Mast cell Stabilizers—Cromolyn, nedocromil
mometasone – Inhibit exercise induced bronchospasm
– Treatment of choice for persistent asthma – Can be used in combination of SABA for
– Improve lung function exercise induced bronchospasm
– Reduce use of rescue medicines j Theophylline
– Reduce ED visits, hospitalizations – Can reduce asthma symptoms and need for
– May lower the risk of death due to asthma SABA use
j Systemic corticosteroids—Prednisolone, – Narrow therapeutic window
prednisone, methyl prednisolone – Not used as first line anymore
– Used mainly in treatment of exacerbations – May be used in corticosteroid dependent
– Rarely in patients with severe disease children
– Long term use can cause adverse effects – Can cause cardiac arrhythmias, seizures and
j Long acting beta agonist—Salmeterol, Formoterol death
– Not used as monotherapy j Anti IgE monoclonal antibody—Omalizumab
– Major role as ad-on agents with ICS – Blocks IgE mediated allergic response
– LABA use should be stopped once optimal – Approved for children >12 years with moderate
asthma control is achieved to severe asthma
j Leukotriene modifying agents – Given subcutaneously every 2–4 weeks
– Leukotriene Receptor Antagonists—
Montelukast (>1 year), Zafirlukast (>5 years)
Choice of Drug therapy in various severity types of pediatric asthma
Less than 5 years More than 5 years

Step 1 (intermittent) Step 1 (intermittent)
• Short acting beta-2-agonists as and • Short acting beta-2-agonists as needed
when needed • If needed more than 2 times/week add preventers
• If Short acting beta-2-agonists is
needed more than 2 times/week,
add preventers
Step 2 (persistent mild) Step 2 (persistent mild)
• Leukotriene receptor antagonist or • Low dose inhaled corticosteroids or Leukotriene receptor antagonist
inhaled corticosteroids low dose
Step 3 (persistent moderate) Step 3 (persistent moderate)
• Low dose inhaled corticosteroids + • Low dose inhaled corticosteroids + leukotriene receptor antagonist
leukotriene receptor antagonist OR
OR • Low dose inhaled corticosteroids + long acting beta-2-agonists
• Double the dose of inhaled OR
corticosteroids • Low dose Inhaled corticosteroids + theophylline sustained release
OR
• Double the dose of inhaled corticosteroids
Step 4 (persistent severe) Step 4 (persistent severe)
• Medium dose of inhaled • Medium dose inhaled corticosteroids + long acting beta-2-agonists
corticosteroids + leukotriene OR
receptor antagonist • Medium dose inhaled corticosteroids + leukotriene receptor antagonist
OR OR
• High dose inhaled corticosteroids • Medium dose Inhaled corticosteroids + theophylline sustained release
• Use oral steroids during acute OR
severe exacerbation • High dose inhaled corticosteroids
Step 5
• Add oral steroids
• Anti-IgE antibody treatment
• Immunotherapy
113
mebooksfree.com
Level of control of Asthma
Parameters Controlled Partly controlled Poorly controlled

Daytime symptoms Less than 2 times/week More than 2 times/week Three or more
Limitations of activities None Any features of partly
controlled asthma
Nocturnal symptoms of disturbed None Any
in any week
sleep
Need for relievers or rescue treatment Less than 2 times/week More than 2 times/week
Lung functions (PEF or FEV1) Normal Less than 80% of
predicted or personal best
Exacerbation None One or more per year One in any week
• Depending on the severity it can be classified into

8.10 Status asthmaticus mild, moderate, severe, and imminent respiratory
arrest
• Severe exacerbation of asthma that does not Classification
improve with standard therapy is termed status • Mild
asthmaticus • Moderate
• Increase in symptoms in the form of cough, • Severe
wheeze, and breathlessness is termed as • Life threatening/imminent respiratory arrest
exacerbation of asthma
Imminent respiratory
Symptoms Mild Moderate Severe arrest
Colour Normal Normal Pale
Sensorium Normal Anxious Agitated Drowsy
Respiratory rate Increased Increased Increased
Dyspnea Absent Moderate Severe
Use of accessory Usually not Commonly Usually Paradoxical thoraco
muscles abdominal movement
Pulse rate/min <100 100–120 >120 Bradycardia
Pulsus paradoxus Absent <10 mmHg Maybe 10–20 mmHg Present Absence suggests
>20–40 mmHg respiratory failure
Rhonchi Moderate Loud Loud and present Absent
throughout
SaO2 >95% 90%–95% <90%
PEFR >70% 40%–69% <40% <25%
Management or CXR showing consolidation) or ventilated

• General measures children
• Allow child to assume most comfortable position. • No role for routine use of mucolytics and
Often sitting upright reduces distress and improves antihistamines
chest wall movement. • Keep NPO till child is stable enough to consume
• Assess ABC and take appropriate steps orally
• Avoid antibiotics except if any evidence of • Start IV Fluids according to the hydration and
infection (high grade fever, purulent sputum, hemodynamic status of the child
114
mebooksfree.com
Drug Mechanism of action and dosage Remarks

Oxygen Treats hypoxia Continuous Spo2 monitoring
Maintain Spo2 >92%
Inhaled beta 2 agonist – Bronchodilator Dilute with 3 mL NS
salbutamol 0.15–0.2 mg/kg (minimum: 2.5 mg) as often as Use spacer
nebulizer every 20 min for 3 doses as needed, then 0.15–
MDI 0.3 mg/kg up to 10 mg every 1–4 h as needed, or
up to 0.5 mg/kg/h by continuous nebulization
Systemic corticosteroids Antiinflammatory Antacids should be added
prednisolone 0.5–1 mg/kg every 6–12 hourly, for 3–7 days Can change to oral once
methyl prednisolone 1–2 mg/kg every 12 hourly patient is stabilized
Anticholinergics Mucolytic/bronchodilator Used as an ‘Add on’ therapy
Ipratropium neb 0.5 mg every 6–8 hourly with Salbutamol
Adrenaline Bronchodilator Poor response to above
1 mg/mL (1:1000) SC/IM (max 0.5 mg) measures indicates impending
if needed repeat after 15–30 min respiratory failure
Theophylline Improves lung function and decreases the need for Monitor serum electrolyte
1 mg/mL ventilation
Loading dose (5 mg/kg over 20 min) and
Maintenance (1 mg/kg/h)
Magnesium sulfate Bronchodilatation Monitor for hypotension and
50% (1 mL = 500 mg) Bolus—25–40 mg/kg (max 2 g) over 20 minutes respiratory depression
ventilated patients with Repeat dose if needed every 12 hourly Maintain magnesium levels
severe wheeze Infusion—30 mg/kg/h between 1.5–2.5 mmol/L
Terbutaline Selective beta agonist Continuous cardio-
1 mg/mL Continuous infusion respiratory/serum potassium
Loading dose (2–10 μg/kg) monitoring required
Maintenance (0.1–0.4 µg/kg/min)
• Indication of intubation • Exercise induced loss of water and heat

j Cardiac arrest from respiratory tract and causes mucosal
j Respiratory arrest hyperosmolarity
j Severe hypoxia not responding to standard • Exercise increases release of chemical mediators from
treatment mast cells
j Rapid deterioration in child’s mental state • Bronchoconstriction leading to increased oxygen
j Progressive exhaustion despite maximal treatment demand and air hunger
• Increased gasping and mouth breathing—
nonhumidified air
8.11 Exercise induced • Airway injury and edema
• Worsening of bronchoconstriction
bronchoconstriction Clinical features
• Paroxysm of cough during exercise
• Also known as exercise induced asthma (EIA)/sports • Decreased respiratory stamina to exercise
asthma • Difficulty in recovery from exertion as compared to
• Airway narrowing as a result of exercise which peer
triggers asthma • Shortness of breath
• Occurs in genetically susceptible individuals with • On examination during the episode—wheezing/
hyper reactive airway prolonged expiration
Pathophysiology Diagnosis
• Exact pathogenesis is not known • Spirometry—normal
• Attack typically occurs after few minutes of starting • Exercise testing—treadmill/ergometer
vigorous aerobic exercise
115
mebooksfree.com
Worsening of FEV1 >15% j Timing the sessions

• Field exercise challenge test—assessing FEV1 after j Step-wise training
exercise Medications
• Eucapnic voluntary hyperventilation challenge—the • Beta 2 agonist 20 min before exercise (most
patient has to voluntarily, without exercising, rapidly commonly used)
breathe dry air enriched with 5% CO2 for 6 min. The • Inhaled corticosteroids/leukotriene antagonists/mast
enriched CO2 compensates for the CO2 lost during cell stabilizers are also effective
hyperventilation and hence CO2 levels normalize. • Vitamin C
• Pharmacological challenge tests: Prognosis
j Methacholine challenge test
j Mannitol inhalation test • Very good
Treatment
• Avoidance of conditions predisposing whenever
possible Please visit MedEnact to access chapter wise MCQs and
Preventive measures previous year pediatrics theory questions asked in various
• Altered training techniques final MBBS University examinations.
j Warm up in increasing intensity
116
mebooksfree.com
Chapter |9|
Rheumatology
• If there are any two of the following:

9.1 Approach a child with j Limitation in range of movements
suspected arthritis j Pain
j Tenderness
j Increased local warmth
• Arthritis is said to be present if there is swelling or
effusion of joint (or)
• Arthritis can be a primary disease condition or
secondary to some other disease
Common causes of arthritis in children

• Avascular necrosis and other • Infections and postinfectious • Drugs
orthopedic conditions, disorders j Pyrazinamide and thiazides
dislocations, slipped capital j Bacterial—Septic arthritis, j MMR vaccine
epiphysis infective endocarditis, • Ehler Danlos syndrome

• Reactive arthritis— tuberculosis, Lyme disease, and other hypermobility
j Reiter arthritis brucella syndromes
j Toxic synovitis of hip j Viral—Rubella, parvovirus, • Systemic connective tissue
• Trauma hepatitis viruses disorders
• Hematological conditions j Poststreptococcal arthritis, j Lupus
j Leukemias rheumatic fever j Dermatomyositis
j Coagulopathies • Tumors j Scleroderma
j Hemoglobinopathies j Benign—Hemangioma, j Henoch–Schonlein
• Rickets and scurvy osteoid osteoma purpura, Kawasaki,

• Juvenile idiopathic arthritis j Malignant—Bone tumors, polyarteritis and other
neuroblastoma vasculitides
Approach to child with arthritis

Age—Age specific Between 2–5 years—Oligo-JIA, Kawasaki disease
presentation of diseases During Adolescence—Lupus, Enthesitis related arthritis
Sex—Several diseases with Females - Oligo-JIA, Lupus
sex preference Males - Ankylosing spondylitis, Enthesitis related arthritis
Duration of symptoms Hours—Trauma, hemophilia
Days—Septic or reactive arthritis
Weeks—Vasculitides, connective tissue disorders, indolent infections
Months—Juvenile idiopathic arthritis
Years—Pain syndromes like reflex sympathetic dystrophy, genetic disorders
117
mebooksfree.com
Onset Explosive and sudden—Septic arthritis, transient synovitis of hip

Insidious: connective tissue disorders
Diurnal variation in Morning stiffness or pain after rest (gelling phenomenon)—Inflammatory disease
symptoms Evening pains after physical activity improving with rest—Mechanical pain
Pattern of joint Solitary—Infections or tumors
involvement Additive—Reactive arthritis
Migratory—Rheumatic fever
Intermittent—Lupus, sickle, hemophilia
Constitutional features Presence in inflammatory pathology (exception of most types of JIA)
like fever, fatigue, and Absence is typical of noninflammatory or mechanical disorders
malaise
Antecedent events or Trauma, recent viral or bacterial infections or recent dysentery, recent immunization
drugs (MMR) reactive arthritis, drugs (pyrazinamide)
Known previous Sickle cell disease or hemophilia, structural heart disease (infective endocarditis and
conditions septic emboli, Down syndrome, Perthe’s disease)
Consanguinity Autosomal recessive conditions sickle, periodic fever syndromes, bony dysplasias
Family history Similar disease-genetic syndromes, spine/eye/joint disease—HLA B27-related
arthropathies, psoriatic arthritis
Musculoskeletal examination • Psoriasis in skin—Psoriatic arthritis

Articular versus periarticular involvement • Alopecia, malar rash, serositis—SLE
• Pain on active and passive movement with swelling • Subcutaneous nodules—Rheumatic arthritis
and instability—Articular • Wasting/contractures—JIA
• Pain on active movement only—Periarticular • Livedo reticularis—Vasculitides
Inflammatory versus mechanical disease • Urethritis—Reactive, Reiter syndrome
• Warmth, erythema, swelling, and tenderness—
Inflammatory
• Lack of these symptoms—Mechanical 9.2 Juvenile idiopathic arthritis
Pointers to chronicity (JIA)
• Pigmentation over joints
• Presence of deformity and contractures • Previously known as Juvenile rheumatoid arthritis
Joints involved specific to certain disease • JIA includes group of idiopathic, chronic inflammatory
• Distal interphalangeal joint—Psoriasis diseases, involving one or more joints associated
• Large joints of the lower limb—Reactive arthritis with other systemic manifestations. These conditions
• Temporomandibular joint—Polyarticular JIA characterized by chronic inflammatory changes in
Number and size of joint joints and symptoms related to inflammation.
• Large joints—Rheumatic fever • JIA is clinically defined as:
• Polyarticular and oligoarticular (SoJIA, psoriatic, j Joint swelling involving one or more joints
leukemia) j Onset below the age of 16 years
Symmetry of involvement j Symptoms persisting for at least 6 weeks
• Symmetrical—Polyarticular JIA, connective tissue
diseases, and vasculitides Etiology
• Asymmetrical—Oligoarticular JIA, enthesitis-related • Exact etiopathogenesis remains unknown. It is
arthritis, and septic arthritis believed to involve complex interaction of multiple
Spine involvement factors like genetic predisposition and inflammatory
mechanisms
• Involved in polyarticular arthritis, systemic onset
juvenile arthritis and sacroiliitis • Major histocompatibility complex (MHC) antigens
associated with JIA are
• Other rheumatological conditions seldom affect
spine j HLA DR5, DR6, DR8—Early onset oligoarthritis
Extra articular manifestations j HLA B27, rheumatoid factor, DR4, DW4, DR1—
Several extra articular are present in various conditions Late onset oligoarthritis
with arthritis. • Proinflammatory cytokines secreted from activated
T cells and macrophages resulting in inflammatory
• Uveitis—Oligoarticular JIA, enthesitis related arthritis arthritis
118
mebooksfree.com
Rheumatology Chapter |9|
• Possible triggering factors Polyarthritis • Accounts for 5%–10% cases

j Infections with Rubella, Parvovirus, Mycobacterium RF positive • Arthritis affecting ≥5 joints during
tuberculosis, Mycoplasma pneumoniae the first 6 months of disease with
j Physical trauma rheumatoid factor positive on two
j Psychological stress occasions at least 3 months apart
• Systemic onset type is believed to be an auto- Psoriatic • Accounts for 2%–15% cases
inflammatory syndrome, disorder of innate immunity arthritis • Arthritis and psoriasis or arthritis
involving cytokines like IL-1, IL-6, IL-18, and cells like and at least two of the following
neutrophils and macrophages. j Psoriasis in a first degree relative
Clinical features and diagnostic criteria j Dactylitis
j Nail pitting or onycholysis

• Onset may be acute or insidious with variable
severity. Most common presentation is symmetrical Enthesitis- • Accounts for 1%–7% cases
involvement of both small and large joints. related • Arthritis and enthesitis or arthritis
Commonly involved joints include proximal and arthritis or enthesitis with at least two of
distal interphalangeal joints, wrists, TM joints, ankles, the following
j Sacroiliac joint tenderness
knees, hips, and cervical spine. Involved joints are
j Presence of HLA-B27 antigen
swollen, warm, and tender. Joint mobility is limited
j Onset >6 years of age in boys
and is kept in flexion. Contractures may develop late
j Anterior uveitis
in the course.
j History of arthritis in 1st
• Systemic type presents with prolonged remittent degree relative
fever, transient morbilliform rash involving the trunk,
muscle aches, weight loss, iridocyclitis, generalized Undifferenti- • Not fitting in any category or
lymphadenopathy, and hepatosplenomegaly. ated arthritis fulfilling criteria of ≥2 categories
• JIA with acute febrile onset and systemic involvement
is termed as Still disease. It is characterized by Investigations
Still triad of arthritis, lymphadenopathy, and • JIA is essentially a clinical diagnosis. Lab
splenomegaly. investigations are of supplementary value and to rule
• Other features include subcutaneous nodules, out differential diagnosis
pericarditis, myocarditis, pneumonia, and pleurisy. • Complete blood count—Anemia of chronic disease.
Polymorphonuclear leukocytosis and thrombocytosis
Updated classification of JIA by International League in systemic onset type
of Associations for Rheumatology (ILAR) • ESR, CRP—Shows mild elevation
Systemic • Accounts for 10%–20% cases • Serology for rheumatoid factor, antinuclear
arthritis • Presence of fever for at least 2 antibodies, HLA B27
weeks duration (with at least 3 • Plain X-ray and ultrasonography show effusions
consecutive days of fever) and • Synovial fluid aspiration for microscopy to rule out
arthritis in ≥1 joints, plus one of septic arthritis
the following • Echo heart to rule out pericardial involvement
j Evanescent erythematous rash
j Generalized lymphadenopathy
X-ray findings in JIA
j Hepatosplenomegaly
j Serositis
Early findings Late findings
Oligoarthritis • Accounts for 50%–60% cases • Swelling of periarticular • Destruction of
• Arthritis affecting 1–4 joints during soft tissue articular cartilages.
the first 6 months of the disease • Joint effusion • Narrowing of the
j Persistent oligoarthritis— • Increase in the joint spaces joint space.
affecting ≤4 joints throughout • Increase in size of • Osteoporosis and
the disease course ossification centers bone deformities.
j Extended oligoarthritis— • Accelerated epiphyseal • Cervical
affecting >4 joints after the 1st maturation spondylitis.
disease • Excessive longitudinal
bone growth
Polyarthritis • Accounts for 20%–30% cases
RF Negative j Arthritis affecting ≥5 joints
Differential diagnosis
during the first 6 months of
the disease • Rheumatic fever
j Rheumatoid factor negative
• SLE, leukemia
• Ulcerative colitis, tuberculosis
119
mebooksfree.com
Treatment Complications
General measures • Uveitis
• Appropriate positioning and rest for the involved • Growth retardation and deformities
joints. Though bed rest is advised in acute phase, • Macrophage activation syndrome
simultaneous minimal exercise once or twice daily is • Anemia
started to prevent contractures • Secondary amyloidosis
• Hot water bath can reduce pain • Subcapsular cataracts
• Treatment of associated infections Prognosis
• Emotional support due to the chronic nature of illness • Oligo arthritis type has good prognosis
Medical therapy • Enthesitis related arthritis can develop sacroiliitis and
• There is no cure for JIA. Medical therapy is aimed at spondylitis
suppressing active disease, preserving joint function, • Rheumatoid factor positive polyarthritis show erosive
reducing pain, preventing long term joint damage and deforming arthritis
and to ensure adequate growth. • Prognosis is better for seronegative polyarthritis
• Disease modifying anti rheumatic drugs (DMARDs) • Systemic onset JIA has variable prognosis and 50%
are used earlier in the course of illness to achieve best will have residual joint involvement and remaining
results will have progressive arthritis
j Methotrexate, sulfasalazine, leflunomideand • Untreated patients develop contractures of hip, knee,
hyroxychloroquine are used in children and elbows resulting in permanent disability
• NSAIDs were first-line treatment earlier but has been
replaced by DMARDs
j Naproxen and ibuprofen are the NSAIDs used in 9.3 Systemic lupus erythematosus
children. Their antiinflammatory dose is usually (SLE)
2–3 times the analgesic dose. Response is usually
seen after 3–4 weeks of therapy. A 3–4 months
therapy is required before switching to another • SLE is a chronic multisystem autoimmune collagen
drug. Indomethacin is particularly preferred in vascular disease predominantly seen in girls
enthesitis related arthritis • SLE is relatively rare in children when compared with
• Corticosteroids are indicated in the presence of adults
carditis, pericarditis, pleuritis, and iridocyclitis and in • Immune dysregulation leads to formation of excess
other life-threatening situations. autoantibodies directed against self-antigens
• Intra articular injection of glucocorticoids are • Deposition of immune complex leads to inflammatory
preferred in oligoarthritis changes in skin, kidney, blood vessels, and nervous
• Newer biological drugs system
j Anakinra (IL-1 receptor antagonist) Etiopathogenesis
j Canakinumab (monoclonal antibody to IL-1) • Exact etiology not known
j Tocilizumab (monoclonal antibody to IL-6 • Various factors like genetic, environmental,
receptor) hormonal, B- and T-cell interactions and role of
j Infliximab, gloimumab, adalimumab (monoclonal dendritic cell and abnormal apoptosis contribute to
antibody to TNF α) development of immune dysregulation
j Etanercept (recombinant soluble TNF receptor • Autoantibodies are formed against DNA and nuclear
p75 fusion protein) antigens, various tissue antigens and blood cells
j Abatacept (inhibitor of T cell activation) • Triggering factors include sunlight, viral infections
• Azathioprine, cyclophosphamide, cyclosporine, anti- and drugs like procainamide, hydralazine, and
TNF agents, interleukin-1 receptor antagonists, and anticonvulsants
IVIG are reserved for refractory cases not responding • Antinuclear antibodies are present in almost all
to first line therapy. patients
• Autologous stem cell transplant in refractory cases • Antibodies directed against double-stranded DNA
(anti-DS-DNA) raised in active lupus nephritis
Treatment of specific types of JIA
• Antibodies to histones are seen in drug-induced lupus
Oligoarticular type NSAIDs + intra-articular • Extensive fibrinoid degeneration and necrosis are
steroids pathological hallmarks of SLE
Polyarticular type DMARDs ± NSAIDs ± Bridging • Presence of lupus erythematosus (LE) cell in the bone
dose of steroids marrow. This cell is polymorphonuclear leukocyte
which contains metachromatic inclusion body which
Systemic onset type NSAIDs + systemic steroids
displaces the nucleus.
120
mebooksfree.com
Leukopenia, thrombocytopenia
j
Deep vein thrombosis

j
• Musculoskeletal manifestations
j Arthralgia and nonerosive arthritis
j Avascular necrosis
j Bone-fragility fractures
j Secondary pain amplification
• Gastrointestinal involvement
j Abdominal pain
j Abdominal vessel vasculitis ± bowel perforation
j Sterile peritonitis
j Pancreatitis
Figure 9.1 Malar rash. Laboratory investigations
• Hemoglobin, WBC total and differential count,
platelets, ESR, and CRP
Clinical features • Urea, creatinine, liver function tests, and lipid profile
• Multisystem disease that does not spare any organ. • Mantoux test and chest radiograph
The onset is gradual with prolonged, irregular fever • Urine routine and microscopy
with remissions of variable duration along with joint, • Specific tests:
renal, and visceral involvement. Classical triads of j ANA, anti-ds-DNA, C3, and C4
clinical features include fever, arthritis, and skin rash. • Anti-Ro/SSA and anti-La/SSB causing congenital heart
• Characteristic butterfly rash involving bridge of nose, blocks seen in neonatal lupus syndrome
lower eyelid and cheek (Fig. 9.1). Rash may also appear • Antihistone antibodies seen in drug-induced lupus
on fingers and palms, soles, palate, and buccal mucosa. (isoniazid, hydralazine, phenytoin)
• Arthritis is polyarticular, nondeforming and can • Anti-Sm antibodies seen in CNS lupus
involve both large and small joints
ACR (1997) Criteria for diagnosis of SLE
• Visceral involvement: Lymphadenopathy and
Hepatosplenomegaly 1 Malar rash
• Mucocutaneous lesions 2 Discoid rash
j Purpura, alopecia
3 Photosensitivity rash
j Photosensitive rash
j Palatal and various vasculitic ulcers 4 Oral/Nasolabial ulcers
j Livedo reticularis, Raynaud phenomenon 5 Arthritis—Nonerosive type
j Cutaneous vasculitis 6 Serositis—Pleuritis, pericarditis
• Renal manifestations 7 Renal disorder:
j Asymptomatic microscopic hematuria Proteinuria >500 mg/24 h or cellular cast in
j Edema, fluid retention, hypertension urine
j Rapidly progressive glomerulonephritis Cellular casts
j Acute renal failure
8 Hematologic disorder:
• Neurological manifestations Hemolytic anemia, thrombocytopenia,
j Seizures, Stroke leukopenia, lymphopenia
j Aseptic meningitis
9 Neurologic involvement—Seizures, psychosis
j Transverse myelitis, peripheral neuropathy
j Neuropsychiatric syndromes (anxiety, mood 10 Immunologic disorder—Positive anti-ds-DNA,
disorder, psychosis) anti-Sm, antiphospholipid antibody
j Guillain–Barré syndrome 11 Raised antinuclear antibody titers
• Cardiac manifestations
Myocarditis
• Any four or more of the above 11 criteria should be
j
Verrucous endocarditis (Libman–Sacks disease)

present either serially or simultaneously
j
Coronary artery disease

Management
j
• Pulmonary manifestations • Avoid precipitating factors like sun exposure, viral

Pulmonary infiltrates
infections, and certain drugs
j
Pulmonary hemorrhage
• Asymptomatic patients need close monitoring and
j
Pleuritis
follow-up. No treatment required.
j
• Hematological manifestations • Mild disease without systemic involvement—

Coomb positive hemolytic anemia
Analgesics and NSAIDs like naproxen
j
121
mebooksfree.com
• Skin lesions and musculoskeletal problems—

Hydroxychloroquine 5 mg/kg/day
• Serositis—Low dose steroid, Prednisolone started at
0.3–0.5 mg/kg/day for 4–6 weeks and then tapered
• Severe disease with involvement of kidneys, blood,
CNS or lung—High dose prednisolone 1–2 mg /kg/
day in divided doses till symptoms subside, followed
by alternate day dose for 4–6 weeks
• Acutely ill and toxic patients are treated with IV
methylprednisolone 30 mg/kg/day for 3 days and
then switched to oral prednisolone
• IV antibiotics if infection is suspected or confirmed
• Other drugs
j Cyclophosphamide—Renal involvement of grade
III and IV
j Mycophenolate mofetil—Lupus nephritis
Figure 9.2 Heliotrope rash.
j Rituximab (anti CD 20) —drug resistant lupus
nephritis
j Azathioprine—Steroid resistant cases • Upper respiratory symptoms predominate but
Complications one-third of patients have gastrointestinal symptoms
• Due to disease • Possible infectious triggers include Group A
j High-risk for end organ damage and failure of streptococcus, upper respiratory infections,
various vital organs like kidneys, CNS, and heart GI infections, coxsackie virus B, toxoplasma,
j Premature atherosclerosis enteroviruses, and parvovirus B19
j Malignancy Clinical features
• Due to treatment • Common clinical presentation includes insidious
j Severe infection and infertility onset fever, erythematous rash, skin, and
j Avascular necrosis of femoral head musculoskeletal symptoms.
j Thrombosis • Fever, arthritis, dysphagia, or dysphonia
j Pulmonary hemorrhage • Photosensitivity to ultraviolet light in sun-exposed
Prognosis areas. Insidious onset of rash involving bridge of the
• With good medical management, 5 years survival rate nose and around eyes (Heliotrope rash) and may
for pediatric SLE is ∼95% and 10 years survival rate is spread to involve trunk and limbs (Fig. 9.2). Shawl
∼80%–90% sign if erythema is seen in neck, upper chest or back
• Common causes of mortality in pediatric SLE or V-sign when present above the breasts
includes lupus nephritis, myocarditis, and CNS • Involved muscles become firm, atrophic and
involvement contracted.
• Face may become expressionless and difficulty in
opening the mouth
9.4 Juvenile dermatomyositis • Gottron papules—bright red thickened or atrophic
plaques over the proximal interphalangeal joints and
• Rare idiopathic chronic inflammatory disease distal interphalangeal joints of fingers and toes
predominantly affecting skin, subcutaneous tissue • Mechanic’s hands—thickened erythematous and
and muscles. The basic pathology involves vessels, scaly rash over the palms
leading to arteritis and phlebitis • Lipodystrophy and calcinosis
• This condition is characterized by: Investigations
j Nonsuppurative inflammation of striated muscle • Elevated serum levels of muscle-derived enzymes
and skin • ESR is normal and rheumatoid factor is negative
j Systemic vasculopathy • Anti nuclear antibody is positive in >80% patients
Etiology • Calcinosis is seen easily on radiographs
• Multifactorial • MRI shows
• Associated with Human leukocyte antigen (HLA) j Muscle edema and inflammation on T2 weighted
alleles like B8, DRB1, DQA1 images
• History of infection 3 months prior to the disease is j Atrophy, fibrosis, fatty infiltration on T1 weighted
present images
122
mebooksfree.com
Diagnosis • More common in boys than girls

• Presence of characteristic rash, as well as at • Significant cause of acquired heart disease in
least three signs of muscle inflammation and children
weakness Etiopathogenesis
• Exact pathogenesis is not known
Classic rash • Heliotrope rash of the eyelids • Current evidence from epidemiologic studies support
• Gottron papules an infectious origin
Plus 3 or more of the following • Kawasaki disease predominantly affects the medium-
Weakness • Symmetric Proximal muscle size arteries like coronary arteries, popliteal and
Muscle enzyme • Creatine kinase brachial arteries
elevation (≥1) Aspartate aminotransferase • Three well defined phases of arteriopathy is seen in
Lactate dehydrogenase kawasaki disease
Aldolase j Neutrophilic necrotizing arteritis occurring in the
Electromyographic • Evidence of myopathy first 2 weeks of illness. Saccular aneurysms may
changes occur during this phase
j Subacute/chronic vasculitis mediated by
Muscle biopsy • Necrosis and inflammation
lymphocytes, plasma cells and eosinophils.
Fusiform aneurysms can result from this arteritis
Treatment j Late phase characterized by predominant smooth
• Corticosteroids are mainstay of treatment muscle cell myofibroblasts proliferation leading
j Intravenous methylprednisolone for 3–5 pulses on to progressive stenosis. Thrombi may form
followed by oral prednisolone and obstruct the blood flow
• Azathioprine or methotrexate are tried when Clinical features
response to steroids are not satisfactory • The disease is characterized by prolonged high
• Hydroxychloroquine used as secondary disease fever, conjunctivitis, stomatitis, cervical adenopathy,
modifying agent to reduce rash and maintain erythema of palms and soles followed by
remission desquamation of digits. The disease often runs a self-
• Duration of therapy is 18–24 months limiting course with average duration of 12 days
• Severe unresponsive disease include intravenous • Gastro intestinal symptoms like vomiting, diarrhea,
immunoglobulin, mycophenolate mofetil, and abdominal pain
cyclosporine, and cyclophosphamide • Respiratory symptoms like rhinnorhea, cough
• Long term prognosis is excellent • Irritability and aseptic meningitis
• Perineal accentuation of the rash with desquamation
• Erythema and induration at BCG scar site
Diagnostic criteria
9.5 Vasculitis 1. Fever lasting for 5 days or more, and
2. Presence of at least four of the following five
Classification of vaculitis in children principal criteria
• Large vessel vasculitis a. Bilateral nonpurulent conjunctivitis
j Takayasu arteritis b. Redness of the oropharyngeal mucosa, strawberry
j Giant cell arteritis tongue (Fig. 9.3), dry fissured lips
• Medium vessel vasculitis c. Edema and erythema of hands and feet,
j Kawasaki disease periungual desquamation involving palms
j Polyarteritis nodosa and soles
• Small vessel vasculitis d. Polymorphous nonvesicular rash
j Anaphylactoid purpura e. Cervical lymphadenopathy of at least 1.5 cm in
j Wegener granulomatosis size usually unilateral
j Behcet disease 3. Illness not explained by another known disease
j Hypersensitivity angitis Investigations
• No specific test to diagnose Kawasaki disease
• Elevated ESR
9.5.1 Kawasaki disease • Hemogram
• Acute onset febrile mucocutaneous lymph node j Normocytic normochromic anemia
syndrome of unknown etiology primarily affecting j Polymorphonuclear leukocytosis
children below 5 years j Thrombocytosis (after the first week of illness)
123
mebooksfree.com
thrombosis, and myocardial infarction can be

present.
• Kawasaki disease can cause premature atherogenesis
in affected coronary artery
9.5.2 Takayasu arteritis

• Chronic large vessel vasculitis
• Also known as pulseless disease
• Age at onset is usually between 10 and 40 years
• Female to male ratio is 2–4:1
Pathogenesis
• Commonly affected vessels are renal, subclavian, and
carotid arteries
• Infiltration of affected vessels by T cells, NK cells,
plasma cells, and macrophages
• Giant cells and granulomatous inflammation develop
in the tunica media of blood vessels
• Persisting inflammation leads to damage of elastic
lamina, in turn leads to dilatation of blood vessels
and formation of aneurysms
• Progressive scarring leads to stenotic or occluded
vessel
Figure 9.3 Strawberry tongue. Clinical features
• Initial presenting symptoms include fever, weight
• Antistreptolysin O titer, ANA and serological tests for loss, malaise, headache, hypertension, arthralgia, and
various infections are negative abdominal pain
• Mild elevations of the hepatic transaminases, Sterile • Late manifestations include weak pulses, asymmetric
pyuria, and proteinuria blood pressures, claudication, and raynaud
• ECG abnormalities are decreased voltage, ST-T phenomenon
changes and conduction defects • Renal artery involvement can lead to renal failure
• Echocardiography—Coronary artery involvement • Features of pulmonary or cardiac ischemia
(aneurysm formation) and carditis • Supra-diaphragmatic (aortic arch syndrome)
Treatment disease manifests with CNS (stroke, transient
ischemic attack), and cardiac (CCF, palpitations)
• Strict bed rest
symptoms
• Intravenous immunoglobulin and high-dose aspirin
are the treatment of choice • Infra-diaphragmatic involvement (midaortic syndrome)
manifests with hypertension, abdominal bruits, and pain
• IVIG is given as single dose 2 g/kg over 10–12 h or
400 mg/kg/day for 4 days. Diagnostic criteria
• Aspirin (80–100 mg/kg) is given daily in four divided • Angiographic abnormalities (CT or MRI) of the aorta
doses during the acute phase and then tapered to anti or its main branches plus at least one of the following
thrombotic dose of 3–5 mg/kg daily. four features
• Low dose of Aspirin is continued for 6–8 weeks after j Reduced peripheral artery pulses and/or
the active phase subsides. claudication of extremities
• TNF inhibitors like infliximab and etanercept are j Upper and lower limb Blood pressure difference
tried in IVIG-resistant disease greater than 10 mm Hg
Prognosis j Bruits over aorta or its branches
Hypertension
• Early recognition and prompt treatment decreases j
the risk of coronary involvement j Elevated acute phase reactants

• Overall mortality can be reduced to less than 0.3% Investigations
with prompt diagnosis and medical treatment • ESR and CRP are elevated
• Worst prognosis is seen in children with giant • Echocardiography
aneurysms • Conventional arteriography of the aorta and its main
• Residual cardiovascular disease like myocarditis, branches to detect luminal defects
pericarditis, coronary aneurysms, coronary • MR angiography and CT angiography
124
mebooksfree.com
Treatment Diagnostic criteria

• Long term immunosuppression with prednisolone • Presence of either a biopsy showing small and mid-
• When the disease progresses or recurs, methotrexate size artery necrotizing vasculitis or angiographic
or azathioprine is used abnormalities (aneurysms or occlusions) plus at least
• Cyclophosphamide is used in severe/refractory disease two of the following
Complications j Skin involvement
• Stroke j Myalgia/muscle tenderness
• Renal insufficiency j Systemic hypertension
• Myocardial infarction j Abnormal urine analysis and/or impaired renal
• Mesenteric ischemia function
• Limb gangrene j Mononeuropathy or polyneuropathy
j Testicular pain or tenderness
Prognosis
j Features suggestive of vasculitis involving any
• With angioplasty and appropriate stent placement, other major organ systems.
the long-term prognosis is good
Investigations
• Survival for individuals with takayasu arteritis is 93% • Hemogram shows elevations of ESR and CRP, anemia,
at five years and 87% at 10 years
leukocytosis
• Hypergammaglobulinemia
9.5.3 Polyarteritis nodosa • Renal involvement (proteinuria, hematuria)
• Elevated hepatic enzyme may suggest hepatitis
• Uncommon systemic necrotizing vasculitis affecting infection
small and medium-size arteries leading on to • Muscle, testicular, or skin biopsy confirms the
inflammatory lesions in the arterial wall, thrombosis diagnosis. Histopathology shows fibrinoid necrosis
and ischemia in medium sized arteries typically with segmental
• Rare in childhood involvement
• Both sex are affected equally • Angiography to detect aneurysms in renal arteries or
• Mean age of presentation is 9 years celiac axis
Etiopathogenesis Treatment
• Exact cause and pathogenesis are not known. • Prednisolone is the mainstay of therapy
Currently accepted hypothesis includes post • Cyclophosphamide and azathioprine are used in
infectious auto immune response refractory cases.
• Infecting organisms believed to trigger this pathology • Antibiotics are given in case of infectious trigger
includes Group A streptococcus, Chronic hepatitis B, • Antiviral therapy to treat hepatitis if detected
Mycobacterium tuberculosis, EBV, CMV, parvovirus
B19, and Hep C virus Complications
• Immune complexes are thought to play a role • Hypertension
• Thickening and narrowing of involved arteries leading • Chronic renal disease
on to ischemia of end organs • Coronary artery disease
• Mesenteric vasculitis
Clinical features
Prognosis
• Clinical presentation depends on severity of affected
arterioles and location. • Prompt medical therapy prevents long term vascular
complications
• Common features includes fever, weight loss, myalgia,
abdominal pain, skin eruptions, and subcutaneous • Mortality in children is less when compared to adult
nodules disease
• Rash (typically livedo reticularis)
• Hypertension in the absence of renal involvement Online supplementary material:
and congestive heart failure
• Abdominal pain, joint pains, hematuria, and ischemic previous year pediatrics theory questions asked in various
gangrene of limbs.
• Neurological involvement—Seizures, encephalopathy,
focal deficits and peripheral neuropathy.
• Pulmonary vasculature is spared.
125
mebooksfree.com
Chapter | 10 |
Infectious diseases
Effects of fever
10.1 Approach to a child with fever
Beneficial Harmful
• Kills some viruses • Increases metabolic
• Definition of fever: Rectal temperature of 38°C or • Decreases microbial demand, CO2
more multiplication production, O2
• Normal Range: 36.5–37.3°C • Increases WBC activity requirement and
• Diurnal variation: Lowest in the morning and highest • Increase phagocytosis cardiac output
in the evening • Increases inflamma- Precipitates
Pathogenesis tory response • Cardiac failure in
severe anemia, heart
disease
• Pulmonary
insufficiency in
chronic lung diseases
• Metabolic problems in
metabolic disorders
• Febrile seizures.
Causes
Infections Malignancies
• Viral • Leukemia
• Bacterial • Lymphomas
• Fungal Autoimmune diseases
• Parasitic • SLE
• Rickettsial Metabolic diseases
• Chlamydial Medications
• Mycoplasmal • Atropine
• Mycobacterial Immunization
CNS abnormalities Exposure to exces-
• Pontine hemorrhage sive environmental
temperature
Periodic fevers
126
mebooksfree.com
Infectious diseases Chapter | 10 |
History • Immunization: Unimmunized/Postvaccination fever

• Age • Medical history
j Neonate and young infant—signs may be subtle, j Recent hospitalizations
require admission j Blood transfusions, vascular catheters
j Children <3 years—may not localize infection j Any chronic medical conditions
• Duration of fever • Personal—sexual activity, drug abuse
j >7 days—likely to be bacterial than viral • Socio-economic history
• Chills and rigors j Occupation of parents
j Malaria j Food and water sources
j Meningitis • Exposure history
j Tonsillitis j Sick family member, Day care, Pets at home, Travel
j Upper urinary tract infection history
• Specific patterns of fever j Maternal infections—intrauterine, intrapartum,
postnatal
• Continuous Fever • Quotidian fever j Arthropods—ticks, mosquitoes, fleas, lice, flies,
j Sustained fever j Daily fever spikes
mites
j Does not fluctuate j Falciparum malaria
Examination
>0.5–1°C • Tertian fever
• Remittent fever j Occurs on the 1st
• Temperature
j Fluctuates >2.0°C and 3rd days • Heart rate
j Does not touch the j Plasmodium vivax
j Tachycardia usually present
baseline • Quartan fever – For every 1°C, pulse increases by 10
• Intermittent fever j Occurs on the 1st
j Bradycardia
j Touches baseline to and 4th days – Enteric fever, Brucella, Leptospirosis
normal temperature j Plasmodium – Lyme’s disease, Drug fever
• Relapsing fever malariae • Respiratory rate
j Febrile periods • Double quotidian fever • Blood pressure
separated by a j Fever that peaks j Raised BP: Intracranial tension
period of normal twice in 24 h j Hypotension: Septic shock, Dengue shock
temperature > 24 h j Juvenile idiopathic syndrome
• Pel-Ebstein fever arthritis • Oxygen saturation if the child has any increased work
j Type of relapsing • Biphasic fever of breathing
fever j Single illness with
• Rash—Measles, rubella, scrub typhus, Infectious
j Cycle of Febrile 2 distinct febrile mononucleosis
days followed by an periods • Purpura—Meningoccocus
afebrile period j Camelback fever /
• Eschar—Scrub typhus
j Lymphomas saddle back fever
• Pallor—Malaria, infective endocarditis
• Hyperpyrexia j Poliomyelitis,
j Temperatures more Leptospirosis,

• Icterus—Hepatitis, malaria, Leptospirosis, Enteric
fever
than 41°C (105.8°F) Dengue fever, Yellow
are most often as- fever • Lymphadenopathy—infectious mononucleosis, scrub
sociated with a j Rat bite fever (Spiril-
typhus, lymphoma, leukemia etc
j Noninfectious cause lum minus) • Systemic examination
j Central fever, Malig- j African hemorrhagic
j Meningeal signs—meningitis
nant hyperthermia fevers (marburg, j Pneumonia
j Drug fever ebola, and lassa j Hepatosplenomegaly
fevers) Lab evaluation as indicated
• Periodic fever • Blood—CBC, PS, Blood culture, Acute phase reactants
j Regular periodicity
• Urine analysis and culture
—Cyclic neutropenia • Stool analysis and culture
• Serology
• All associated symptoms j Rapid antigen testing
j Vomiting and diarrhea—acute gastroenteritis j Nasopharyngeal: respiratory viruses by polymerase
j Fever with burning micturition—urinary tract chain reaction
infection • Throat: group A Streptococcus
j Fever, red eyes, coryza, rash by 4th day of fever- • Cerebrospinal fluid: cell count, glucose, protein,
measles Gram stain, culture
• Any medications/Fluid intake/Urine output • Chest radiograph, LFT, Renal function tests
127
mebooksfree.com
• Other imaging studies Fever without focus in 1–3 months

Treatment • Etiology
Serious bacterial infection 5%–15%
• Adequate hydration j
– Urinary tract infection –most c

• Antipyretics
j Acetaminophen/paracetamol ommon
– 10–15 mg/kg/dose orally, – Bacteremia
– Not more than every 4-hourly j Viral
– Maximum of 4 doses/day – Enterovirus, Influenza, Parechovirus
j Ibuprofen • Management Approach
– 5–10 mg/kg/dose orally j Several criteria are used to assess if low risk
– 6–8-hourly – Rochester criteria, Boston criteria, Philadelphia
– Maximum of 4 doses/day protocol, Pittsburgh guidelines
– Not recommended for babies < 6 months old j Assessment of Severity - ABCD
j Mefenamic acid – Alertness, Arousal and Activity reduced
– Breathing difficulties—Tachypnea,
• Hydrotherapy/tepid sponging
retractions
• Specific antimicrobial therapy—Antibiotics
– Colour—Pale extremities
– Decreased fluid intake and urine output
j Lab investigations
– Blood culture, Urine culture, CSF culture
10.2 Fever without focus
– CBC, CRP
– Stool culture in dysentery
Definition – CXR if respiratory signs
• Fever (rectal temperature > 38°C) – Serum electrolytes and ABG if red
• Acute onset, Less than 7 days duration flag signs
• No localizing signs j Start IV antibiotics
• In children <36 months of age – Ampicillin + cefotaxime/ceftriaxone
• Classified into 3 broad age groups – Vancomycin if meningitis suspected
j The neonate Fever without focus in 3–36 months
j 29 days—3months age • Causes
j 3–36 months age j Occult bacteremia risk is only 0.5%
Fever without focus in neonates (1–28 days) j Mostly viral
• Etiology j In Hib immunized, S. pneumoniae common
j High risk of serious bacterial infection j Urinary tract infection common
j Bacteremia/sepsis: Group B Streptococcus/E.coli/ • Management Approach
Listeria j Assessing degree of illness
j Meningitis, Pneumonia, Urinary tract infection j Yale observation scale: 16 or more: 92% risk of
j Septic arthritis, Osteomyelitis serious bacterial infection
j Viral: HSV, Enterovirus, Parechovirus Treatment options
j Dehydration fever • Send blood culture for all and start empirical
• Management Approach antibiotics
j All such neonate should be admitted • Is child toxic?
– Following investigations should be done
– CBC, Blood culture, CRP, Micro ESR
– Urine culture, Stool culture
– CXR
– CSF—cell count, glucose and protein, gram
stain and culture
– PCR-HSV, enterovirus
j Empirical IV antibiotics
– Ampicillin + cefotaxime or
– Ampicillin + gentamycin
j Acyclovir if HSV suspected as in
– Maternal genital HSV at delivery
– Seizures, Hypotension
– Increased transaminases, CSF pleocytosis
128
mebooksfree.com
Endocrine Familial
10.3 Pyrexia of unknown origin • Thyrotoxicosis • Ectodermal dysplasia
• Thyroiditis • Familial Mediter-
Definition • Addison’s disease rean fever Muckle
• Single episode of fever Hypersensitive reaction wells syndrome
• Temperature greater than 38.3°C • Drug fever, Serum sickness Miscellaneous
• Cause is not diagnosed • Poisoning,
j with 3 or more weeks of OPD evaluation Kawasaki’s
j with 1 week of in-patient evaluation • Factitious fever
Classification
History
• Classic
j Seen in Infections, Malignancies and Inflammatory
• Age
j Neonate—E.coli, GBS, listeria
conditions
j <6 years—infections more common cause
• Nosocomial
j Temperature > 38.3°C
• Gender
j Male—Bruton’s a gamma globulinemia
j Duration >1 week
j Female—SLE, Pelvic inflammatory disease
Not present and not incubating at admission
• h/o contact with tuberculosis
j
At least 3 days of investigations

• h/o exposure
j
j 2 days of incubation of cultures

j Animals—leptospirosis
j Causes
j Tick—tick bite fever
– Health care associated infections
j Travel—malaria
– Septic thrombophlebitis
– Drug fever
• H/o pica—toxocara, toxoplasma
• Medication—drug fever
• Neutropenic
Temperature > 38.3°C
• Immunization
• Family history—familial fever syndrome
j
j Neutropenic—counts < 500/uL
j At least 3 days of investigations Examination
j 2 days of incubation of cultures • Temperature
• Immune-deficient j Intermittent: Malaria
j Temperature > 38.3°C j Continuous: Miliary TB
j >1 wk duration j Periodic/undulating: Hodgkins, brucellosis.
j Negative cultures after 48 h • Relative bradycardia: Typhoid, Dengue, Weil’s disease
• HIV-associated • Anemia: Malaria, Kala-azar, Endocarditis, Leukemia
j Temperature ≥38.3°C • Clubbing: Lung abscess, bronchiectasis
j >3 weeks for outpatients • Lymph node
j >1 weeks for inpatients j Generalized lymphadenopathy: Hodgkins disease,
j HIV infection confirmed Leukemia, TB
j Localized lymphadenopathy: Glandular fever,
Causes of PUO Scrub typhus
• Jaundice: Infectious hepatitis, Weil’s diseases
Infections Rheumatological
• Rheumatic fever
• Skin rash
• Virus: HIV, CMV
j Viral exanthematous illnesses
• Bacteria: Salmonella, • JRA, SLE
Meningococcemia
• Juvenile
j
Brucellosis, Campylobacter,
dermatomyositis j Dengue
Tuberculosis, Scrub
• Behcet’s disease Rickettsial illness
typhus, Leptospirosis,
j
Lyme disease Neoplasms • Bony tenderness: leukemia

• Fungi: Blastomycosis, • Leukemias, • Eye
cryptococcosis, Lymphoma j Conjunctivitis
Histoplasmosis • Wilm’s tumor, – Bulbar—Leptospirosis, Kawasaki disease
• Parasites: Malaria Neuroblastoma – Palpebral—Coxsackie, infectious mononucleosis
• Localized infections Granulomatous j Uveitis—SLE, JIA
- Sinusitis, Mastoiditis • Crohn’s, Sarcoidosis j Chorioretinitis—TORCH
- Pneumonia, Pyelonephritis Metabolic j Conjunctival hemorrhage—Infective Endocarditis
- Infective endocarditis • Gout, Porphyria j Fundus—Choriod tubercules in tuberculosis
- Osteomyelitis, Abscesses • Sinus tenderness—sinusitis
• Recurrent oral thrush—immunodeficiency
129
mebooksfree.com
Lab Diagnosis Etiology

• Bordetella pertussis, a gram negative bacillus is
Second line the causative organism. The organism is small,
Routine/ first line tests investigations aerobic, fastidious and requires special media for
• Hemogram, Peripheral • Serology—EBV, CMV, isolation.
smear, CRP WIDAL, Brucellosis, • Produces multiple antigenic and biologically active
• Elevated ESR (>30) Leptospira, Scrub products including pertussis toxin, filamentous
—TB, Malignancy, typhus hemagglutinin, agglutinins, adenylate cyclase
Autoimmune disease • Autoimmune studies – pertactin and tracheal cytotoxin.
• Urine and Stool routine, RA factor, ANA • Lifelong immunity follows an episode of natural
occult blood • Imaging studies – B. pertussis infection in most cases.
• Cultures—blood, urine ECHO – vegetations
Epidemiology
and stool of IE, CT, MRI and
• Radiological—chest and Barium studies • It is notifiable disease in India
paranasal sinus • Isotope scans • Number of cases have declined following
• Mantoux test, CSF • Endoscopy and biopsy introduction of vaccine
analysis • Lymphangiography • Coughing adolescents and adults are major reservoirs
• ECG, Liver function test • Exploratory of B. pertussis
• Ultrasonography— laparotomy • Attack rate is as high as 100% in susceptible
Intraabdominal individuals exposed to aerosol droplets
abscesses • Both epidemic and sporadic forms are common
• Biopsy—Liver, Bone Pathogenesis:
marrow, lymph node
• Primarily a toxin mediated disease
Treatment • Bacteria attach to cilia of respiratory epithelial cells.
• Antipyretics • Inflammation occurs which interferes with clearance
of pulmonary secretions.
• Antimicrobials as indicated
• Specific treatment based on diagnosis • Pertussis antigens allow evasion of host defenses
• Major pathogenic factors and their functions
Prognosis and outcome j Filamentous hemagglutinin—Attachment to
• Depends on cause respiratory epithelium
• In 25%—cause is not identified j Lymphocyte promoting factor (LPF)—Causes
Absolute lymphocytosis
j Adenylate cyclase toxin—Inhibits phagocytic
10.4 Bacterial Infections function
j Dermonecrotic toxin—Local epithelial damage
10.4.1 Pertussis j Pertussis toxin—Attachment to epithelium and
phagocytic dysfunction
• Pertussis is an acute highly contagious respiratory j Tracheal cytotoxin—Disrupts mucociliary
tract infection. clearance and damages epithelium
• It is exclusively seen in children Clinical features
• Characterized by catarrhal symptoms followed by • Incubation period: 7–14 days.
bouts of cough and ‘inspiratory whoop’
130
mebooksfree.com
Complications: Prevention
• Secondary bacterial pneumonia-most common • Killed whole cell pertussis (DTwp) or acellular
• Neurological complications—seizures, pertussis (DTaP) vaccine. Whole cell pertussis is
encephalopathy more common among infants contraindicated in progressive neurological disease
• Otitis media, Dehydration, Pneumothorax • Give along with Diptheria and Tetanus (DPT trivalent
• Epistaxis, Subdural hematoma vaccine) or Pentavalent vaccinet (DPT + Hib + Hep B)
• Hernias, Rectal prolapse
Lab Diagnosis:
• Lymphocytic leukocytosis 10.4.2 Staphylococcal infections
• Reduced ESR
• Chest Xray—Perihilar infiltrates, atelectasis or emphysema
Introduction:
• Culture-gold standard (Bordet-gengou medium)—
j Cough plate method—Child is encouraged to • Staph aureus is the most common cause of pyogenic
cough directly over an open culture plate infection of the skin and soft tissue
• Polymerase chain reaction • Bacteremia is common
j Can confirm pertussis in an outbreak • Also causes toxin mediated diseases
j Highly sensitive • Methicillin resistance is a global problem.
j High false positive rate Etiology:
• Serology • Disease may result from tissue invasion or injury
j Can confirm illness late in the course of infection caused by various toxins and enzymes produced by
j Many tests have unproven or unknown clinical the organism.
accuracy
Virulence factors of staphylococcus:
• Direct fluorescent antibody test
j Low sensitivity • Extracellular enzymes—Coagulase, hyaluronidase,
lipase, nuclease, staphylokinase
j Variable specificity
j Should not be used for laboratory confirmation • Toxins—Haemolysins, leucocidin, enterotoxin,TSST,
Exfoliative toxin
Treatment: • Cell associated polymers
• General measures: • Cell surface proteins
j Isolation
j Cough syrups Epidemiology:
j Oxygen supplementation in hypoxia • Many neonates are colonized within the first week
j Maintenance of fluid and nutrition of life
• Antibiotic therapy • Normal individuals colonise Staph aureus in the
j In < 1 month—Azithromycin 10 mg/kg/day in a anterior nares
single dose for 5days • The organisms may be transmitted from nose to skin
j 1–5 months—Azithromycin 10 mg/kg/day in a • Invasive disease may follow colonization
single dose for 5 day(or) Erythromycin 40 mg/kg/ • It is the commonest cause of hospital cross
day in 4 divided doses for 14 days infections.
• Infants aged more than or equal to 6 months Mode of Transmission:
j Azithromycin 10 mg/kg in a single dose on day 1 • Persons with lesions
and 5 mg/kg/day on days 2–5 (or) • Airborne droplets
j Erythromycin 40–50 mg/kg/day in 4 divided • Asymptomatic carrier
doses for 14 days (or) • Cross-infection
j Clarithromycin 15 mg/kg/day in 2 divided doses
Infections caused by Staph aureus:
for 7 days (or)
j Cotrimoxazole—8 mg/kg/day of Trimethoprim + • Superficial infection:
j Skin infection—pustules, boil, carbuncle, abscess,
SMZ 40 mg/kg/day in 2 divided doses for 14 days
styes, impetigo, pemphigus neonatarum, sepsis in
• Older children and Adults
wounds and burns
j Azithromycin 500 mg in a single dose on day 1
then 250 mg/day on days 2 to 5 (or) • Deep infection:
j Bone and joint—Osteomyelitis, septic arthritis
j Erythromycin 2 g/day in 4 divided doses for
j Respiratory tract—Tonsillitis, pharyngitis,
14 days (or)
pneumonia, lung abscess, empyema, suppurative
j Clarithromycin 1 g/day in 2 divided doses for 7
mouth lesions ( dental abscess), localized oral
days(or)
abscess
j TMP—320 mg/day, SMZ-1600 mg/day in 2
j Intestinal—Enterocolitis
divided doses for 14 days
131
mebooksfree.com
j Cardiac—Endocarditis, pericarditis • Most of the strains of Staph aureus were sensitive to

j CNS—Meningitis, brain abscess, shunt infections, penicillin originally
subdural empyema • Soon after penicillin came into use, resistant strains
• Toxin associated infection: began to emerge
j Toxin food poisoning—Ingestion of preformed j Production of beta lactamase
toxin in food j MRSA cause outbreaks of hospital infection
j Skin exfoliation(Staphylococcal Scalded Skin j Vancomycin/teicoplanin is used to treat MRSA
Syndrome—SSSS)—Stripping of superficial layer Treatment of staphylococcal infections:
of skin from underlying tissue by exfoliative
• Antibiotic therapy of staphylococcal infections has
toxin become complicated due to evolving resistance in
j Toxic shock syndrome-TSS is a syndrome staphylococci.
caused by enterotoxin E produced by Staph
• Benzyl penicillin is the most effective in sensitive
aureus strains
Predisposing Factors • Cloxacillin is used against beta lacatmase producing
• Host Factors—breach in skin, chemotaxis defects, strains
opsonization defects, neutrophil functional defects, • Vancomycin is used to treat MRSA infections
presence of foreign bodies • Linezolid/teicoplanin also used to treat MRSA
• Pathogen Factors—catalase, coagulase, infections.
hyaluronidase, lipases, beta lactamases. • For mild superficial lesions, topical application of
• Toxin Shock Syndrome—fever, shock, skin rash, bacitracin or chlorhexidine may be sufficient.
hepatic derangement, sensorial changes and high • Other alternatives are
mortality j 1st generation cephalosporins (cephalexin,
CONS (Coagulase negative staphylococcus aureus) cefadroxil) and 2nd generation cephalosporin
(cefuroxime), coamoxiclav, clindamycin.
• Commonly implicated in bacteremia in low birth j Abscesses must be drained.
weight babies
Control of Staphylococcal Infections
• Also in central venous catheters, subacute
infective endocarditis, CNS shunt infections, • Isolation and treatment
infections associated with peritoneal dialysis • Detection of carriers among hospital staff, their
catheters and prosthetic joints, urinary tract isolation and treatment
infections and postoperative surgical site infections. • Sterlization of instruments
• Staphylococcus saprophyticus: • Stop misuse of antibiotics
j Acts as an opportunistic pathogen • Hand asepsis is the most important measure in
j Causes UTI in young females preventing nosocomial infections.
j Causes septicemia and endocarditis in patients
with cardiac surgery. 10.4.3 Enteric fever (Typhoid fever)
Laboratory diagnosis: • An acute febrile illness characterized by
• Specimens: these are collected according to the constitutional symptoms like prolonged pyrexia,
nature of lesion as follows: hepatosplenomegaly and lymphadenopathy
j Pus-suppurative lesions • Two types of Enteric fever are described
j Sputum-respiratory infections j Typhoid fever—Salmonella enteric var typhi
j Blood-septicemia or PUO j Paratyphoid fever – Salmonella enteric var
j Urine—urinary tract infection paratyphi A,B,C
j CSF- meningitis • Route of transmission—Feco oral route.
j Faeces—food poisoning
Source:
j Food/vomit—food poisoning
• Specimen should be collected in sterile containers • Primary—Cases or carriers
and transported immediately to the lab. • Secondary—Flies, water, food, fingers
• Direct microscopy—Gram stained smears shows gram Etiology:
positive cocci in clusters • Salmonella enterica serotype typhi/paratyphi is a
• Culture—Salt agar/Robertson’s cooked meat medium Gram negative, nonlactose fermenting, flagellate
contains 10% Nacl bacterium.
Antibiotic susceptibility • Significant antigens
Somatic O and Flagellar H antigens
• This is important as staphylococci develop resistance j
to drug easily j Capsular polysaccharide :Vi
132
mebooksfree.com
Infective dose: 103 to 106 organisms • Pneumonia, Ataxia, Encephalopathy

Incubation period: • Disseminated intravascular coagulation
• Children: 8 days Investigations:
• Adults: 10–14 days • CBC: Leucocyte—Normal/Low
Pathophysiology: • Leukopenia with relative lymphocytosis may be seen
in small subset of patients
• Absolute eosinopenia and Neutrophilic predominance
• Anemia, thrombocytopenia
• LFT: SGOT and SGPT—Elevated 2–3 times
• CRP: Elevated—Helps to differentiate from dengue
• Blood culture: Gold standard method
j Positive in 90% cases at first week
j 5 to 10 mL blood in 50 to 100 mL broth
j Clot culture: better yield
j Blood allowed to clot and lysed with streptokinase
j Bone marrow culture if blood culture is negative
• Radiometric methods: BACTEC
• Serology: Widal Test
j Detects Ig G and Ig M antibodies to H antigen and
O antigen
j Single titre of at least 1:160 for O and H is
considered positive
j Conventional method—Four fold rise in Paired
Sera 7 to 10 days apart
• Bone marrow culture
• Others: Typhoid assay, Tubex system, Dipstick
Clinical features: • Newer: Nanotechnology, Typhidot ELISA
• Molecular immunology
First Second Third Fourth • RT PCR
week: week: week: week:
Treatment:
• Fever(low • Gaseous • Typhoid state • Conva-
grade to abdominal • Toxemia lescence Uncomplicated Typhoid Fever
high grade) distension • Apathy Fully sensitive Chloramphenicol, Amoxicillin
• Malaise, • Diarrhea • Delirium Multidrug resistant Fluoroquinolone or cefixime
headache • Rose spots • Encephalopa-
• Sore throat, thy, coma Quinolone resistant Azithromycin or ceftriaxone
nausea • Intestinal Severe/Complicated Typhoid Fever
• Abdominal perforation Fully sensitive Ampicillin or ceftriaxone
pain and
• Pea soup hemorrhage Multidrug resistant Fluoroquinolone
diarrhea occurs in Quinolone resistant Ceftriaxone /Azithromycin
• Hepatosple- terminal
nomegaly ileum/ • Multidrug-resistant strains of S. typhi: Isolates
caecum fully resistant to amoxicillin, trimethoprim-
sulfamethoxazole, and chloramphenicol
• A macular rash appears around fifth day of fever and • Drug dosages
predominantly seen in front and back of the trunk j Cefixime 20 mg/kg/day for 2 weeks
• Relative Bradycardia, a common finding in adults is j Azithromycin (10–20 mg/kg/day)
unusual in children j IV Ceftriaxone and cefotaxime—75–80 mg/kg/
• In children, usually the classical ‘step ladder pattern’ day
is absent and all the stages are shortened. • Duration of Antibiotics
• Chronic carrier: Excretion of typhoid bacilli for more j At least 10 to 14 days
than one year. E.g.,: Typhoid Mary. j Stopped 5–7 days after cases become afebrile
Complication: • Steroids in severe typhoid fever:
• Bleeding/perforation j Indicated in cases of encephalopathy and shock.
• Splenic abscess, Hepatitis, cholecystitis j Can precipitate intestinal perforation
133
mebooksfree.com
Dexamethasone - Initial 3 mg/kg slow IV for

j • Liberates serous and fibrinous material
30 min followed by 1 mg/kg every 6 h • Within 2–3 days, Grayish white pseudo
• Carriers: membrane
j Amoxicillin 100 mg/kg/day with Probenecid • Organ affected: kidney, myocardium
30 mg/kg/day for 6 to 12 weeks Clinical features:
OR

• Presentation depends on the location of membrane,
j Cotrimoxazole10 mg/kg/day. its extent and the age of patient
Prognosis: Relapse in 1–3 weeks after treatment. • Early symptoms include Fever, Malaise, headache
Prevention: • Four specific types are recognized
• Personal hygiene j A) Faucial/Tonsillopharyngeal diphtheria
• Domestic hygiene – Commonest form
• Food and water hygiene – Whitish gray membrane over tonsils. Difficult
• Vaccination: to remove and may cause bleeding and spread
of toxin if attempted.
– Cervical lymphadenopathy
Vi polysaccharide vaccine Ty21a vaccine
– Sore throat, dysphagia
• For IM/SC use • Live attenuated vaccine – Muffled voice
• Not immunogenic in • Induce local gut immunity – Moderate fever and tachycardia
children <2 years • Enteric coated formulation j B) Nasal diphtheria
• Marker: Anti Vi anti- • To children ≥5 years as – Visible membrane over turbinates
bodies capsules – Uni/bilateral serosanguinous nasal discharge
• Does not interfere with • 3 doses on alternate days – Excoriation of upper lip
WIDAL interpretation in empty stomach with – Minimal constitutional symptoms
• Single dose for age cold liquid j C) Laryngotracheal diphtheria
= >2 years • Should not be given
– Life-threatening but less common
• Next dose every 3 years during diarrhea and anti-
– Brassy cough, Stridor
• Vi PS conjugate vaccine: microbials
– Respiratory distress
Available in India but • Not available in India at
not on regular use. present. – Bull neck cervical lymphadenopathy
j D) Cutaneous Diptheria
– Membrane formation on skin, open wounds,
Whole cell inactivated vaccine (TA vaccine) genitalia, and conjunctiva
• Includes heat killed S. typhi an S. paratyphi A – Underlying ulcers are chronic and painless
• Relatively cheap Complications:
• Two doses: 0.25–0.5 mL each subcutaneously at • Airway obstruction: Leads to respiratory failure.
4–6 weeks interval • Myocarditis, arrhythmias, CCF(in 2nd week of
• Vaccine is given above 6 months of age illness)
• Neurological: Palatal palsy, ocular palsy
j Loss of accommodation
10.4.4 Diphtheria j Generalized polyneuritis.
• Acute respiratory illness characterized by • Renal: Oliguria, proteinuria
membrane formation in the upper respiratory Lab diagnosis
tract and toxemic symptoms resulting from the • Diagnosis is primarily clinical
locally released exotoxin. • Hemogram: Neutrophilic leukocytosis and
• Etiology: Caused by Corynebacterium diphtheria, thrombocytopenia
gram positive, pleomorphic bacillus that grows on • Albert stain of swab from oropharynx /larynx
Loeffler’s medium shows Chinese letter/Cuneiform pattern
• Source: Droplet Secretions/discharges from carriers/ (Fig. 10.1)
infected persons • Other stains used: Neissers stain, Ponders stain
• Portal of entry: Respiratory tract • Culture: Loeffler’s medium and tellurite blood agar.
• Incubation period: 2 to 5 days • Fluorescent antibody detection
• Predominantly seen during winter months Treatment:
Pathogenesis • Supportive: Airway, breathing, circulation
• It is a toxin mediated disease. j Intubation, Tracheostomy to secure airway in
• C. diphtheria liberates a powerful exotoxin laryngeal form
• Necrosis of epithelial cells j Bed rest, cough medications and antipyretics
134
mebooksfree.com
j Catch up < 7 years: DTwP/DtaP at 0, 1, and

6 months
j Catch up >7 years: Tdap, Td at 0, 1, and
6 months
j Should never be frozen
j Protective titre: > 0.1 IU/mL for diphtheria
j Dose: 0.5 mL IM in Anterolateral aspect of thigh
j Immunity: 80% for diphtheria
j Absolute contraindication:
– H/o anaphylaxis
– Development of encephalopathy within 7 days
following previous DTwP vaccine.
10.4.5 Scrub typhus

Figure 10.1 Chinese letter pattern seen in Albert’s stain. • Scrub typhus is an acute febrile, infectious illness.
• More commonly seen in Jammu and Kashmir,
Himachal Pradesh, Rajasthan, Assam, Kerala, and
• Administration of antitoxin: IM/IV route Tamil Nadu.
j Antidiphtheritic serum (ADS) 20,000–100,000 • Causative agent: Orientia tsutsugamushi
units • Vector: Trombiculid mite (Leptotrombidium
j Dose depends on site, extent of membrane and deliense)
degree of toxemia • Mode of transmission: Transmitted by bite of vector
j Neutralizes only free toxin not bound to tissues. (often painless)
j Sensitivity testing is done prior to administration • Incubation period: 6 to 20 days (average 10 days)
due to risk of anaphylaxis Pathogenesis:
• Antibiotics: Penicillin, Amoxcillin, Erythromycin for • Local eschar formation at the site of mite bite (chigger
2 weeks
larval stage)
• Active immunization: As clinical disease does not • Organisms spread to local lymph nodes initially
confer active immunity.
followed by blood stream invasion affecting
Recommend ADS dosage endothelial lining of blood vessels in various
organs.
Type of involvement Dosage (in units)
• Invasion of endothelial layer of vasculature and
Laryngeal or pharyngeal 20,000 to 40,000 subsequent microvasculitis leading on to
involvement of less than 48 h j Increased vascular permeability and edema
duration j Loss of blood volume
Nasopharyngeal involvement 40,000 to 60,000 j Hypoalbuminemia and reduced osmotic pressure
Extensive disease over 3 days 80,000 to 100,000 j Hypotension
duration or with brawny neck Clinical features:
edema
• Initial symptoms include sudden onset high grade
fever, headache, myalgia, anorexia and conjunctival
injection.
Prevention and control:
• Isolation till 2 successive culture: negative • Hepatosplenomegaly
• Chemoprophylaxis: • Small (0.1 to 2 cm) painless gradually enlarging
papule usually seen in trunk area which leads to
j Oral erythromycin 7 days or single dose
area of black central necrosis, known as eschar
benzathine penicillin.
(Fig. 10.2). It signifies the site of mite bite. Often
j For household and other contacts.
found in skin folds of axilla, groin, neck, behind
• Vaccination: ears etc.
j Diphtheria, Tetanus toxoid and Pertussis vaccine
j Now as pentavalent vaccine (DPT + Hep B + Hib)
• Eschar is associated with tender regional
lymphadenopathy in > 80% cases
j Minimum age: 6 weeks
j Standard schedule: Complications:
– At 6, 10, and 14 weeks • Pneumonia, Acute liver failure
– 2 boosters—15 to 18 months and 5 years • Meningismus/Encephalopathy
135
mebooksfree.com
• Daily inspection of body for mites is particularly

important
10.4.6 Tetanus
• Acute infection caused by Clostridium tetani
characterized by the triad of rigidity, muscle spasms
and autonomic instability
• Symptoms are due to powerful exotoxin released by
organism that leads to reflex muscle spasm and tonic
clonic convulsion.
• Causative agent: C. tetani, anaerobic, spore forming,
gram positive bacilli
• Mode of transmission: Crush devitalized wounds,
wounds with anaerobic environment in the tissues,
contamination of wound.
• Incubation period: Usually 7 to 10 days. Shorter the
incubation period associated with severe disease and
worse prognosis
• Exotoxins released by C. tetani:
Tetanospasmin is a neurotoxin and is responsible
Figure 10.2 Eschar of scrub typhus.
j
for the clinical signs and symptoms of the

disease.
• Pulmonary edema, Myocarditis j Tetanolysin causes hemolysis
• Acute renal failure, DIC
• Pathogenesis:
Supportive diagnosis:
• Early lymphopenia with late lymphocytosis
• Thrombocytopenia
• Elevated transaminase level
• Hypoalbuminemia
Definitive diagnosis:
• IgM or IgG antibody detection by ELISA (Positive
titre > 0.5 OD)
• Indirect immunoperoxidase test
• Indirect fluorescent antibody test
• Rapid immunochromatographic tests for detection of
IgM and IgG
• PCR
• Weil felix OX-K strain agglutination reaction
Treatment:
• Azithromycin is the drug of choice for less than 8 years
old children. Dose (10–20 mg/kg/day OD) × 5 days Clinical features
• Cap. Doxycycline is used in children above 8 years. • Localized tetanus
Dose—4 mg/kg/day × 7days. j Spasm and pain in proximity to site of injury
• Chloramphenicol or Rifampicin can be used in j Infection restricted to local are with no CNS
case of doxycycline allergy(50–100 mg/kg/day i.v. involvement
every 6 h) j Occurs when concentration of tetanospasmin
• Current guidelines recommend Doxycycline as first released is low
line drug for all ages j Usually recovers completely without any
complication
Prevention:
• Cephalic Tetanus
• Protective clothing j Rare variant of localized tetanus
• Insect repellents j Seen in children with otitis media.
• Chemoprophylaxis should be started with j Site of invasion is in the head, neck or face
Doxycycline while travelling to endemic area j Can present with multiple cranial nerve palsies
136
mebooksfree.com
• Generalised tetanus: be given intravenously in four divided doses for

j Most common form (seen in >80% cases) 10–14 days.
j Characteristically there is descending paralysis • Ryle’s tube has to be passed to prevent aspiration but
with initial involvement of jaw muscles. later for feeding purpose.
j Spasm of masseter muscle leads to ’Lockjaw or • Muscle relaxant requires in all patients of generalized
Trismus’. tetanus. Diazepam causes both muscle relaxation and
j Rigidity of facial muscles leads to typical grin, seizure control. Diazepam 0.1–0.2 mg/kg every 3–6 h
sardonic smile of tetanus or risus sardonicus given intravenously.
j Spasm of back and abdominal muscles leading to • Maintenance of fluid and electrolyte homeostasis
arching (opisthotonus). • Autonomic instability is treated with propranolol and
j As the disease progress, even minimal stimuli can labetalol.
lead to generalized spasm which are hallmark of • Local wound care, surgical debridement and topical
disease antibiotics if needed.
j Sensorium is usually intact till late stages. • I.V magnesium is effective in decreasing autonomic
j Airway obstruction can occur due to spasm of instability and treating muscle spasm.
laryngeal muscles.
j Autonomic instability due to sympathetic 10.4.7 Leptospirosis
nerve involvement such as hypertension,
excessive sweating, arrhythmias, tachycardia, • Acute infectious disease caused by Leptospira
interrogans
hyperpyrexia.
j Recovery begins after 3 weeks. • Most severe—Serovar L. ictero hemorrhagiae
• Neonatal Tetanus: Aetiopathogenesis
j Occurs in newborn born to pregnant women who • Rat is main source of infection
are not immunized against tetanus • Water contaminated with rat urine
j Causes: • Others—dogs, cats, livestock
– Unhygienic and improper handling of the • Infected through abraded skin and mucous membranes
umbilical cord in newborns, • Damage to the endothelial lining of small blood
– Lack of hygienic habits vessels
– Poor aseptic care during delivery • Ischemic damage to the liver, kidneys, meninges,
j Symptoms appear by 3rd to 12th days of life. muscles
j Initial symptoms include irritability, excessive • Anicteric leptospirosis (common, less severe)
crying, refusal of feeds, feeding difficulty and apathy. • Icteric leptospirosis (rare, but severe)
Appearance of rigidity, paralysis and opisthotonus
j
• Incubation period: 4–19days
posturing. Clinical features
j Stimuli such as touch, noise, bright light can Anicteric Leptospirosis
lead to spasm of larynx and respiratory muscles
resulting in apnea and cyanosis. • Biphasic illness
j Spasm of pharyngeal muscles causing dysphagia, • First phase–septicemic phase–multiplication of
choking followed by spasm of extremity muscles. leptospira in bloodstream
• Second phase-immune phase-antibodies to leptospira
Treatment develop
• Principles of treatment • First Septicemic Phase–lasts 4 to 7 days
j Airway maintenance—Intubation and mechanical Fever, chills
j
ventilation may be required Myalgia, headache
j
j Prevention of further toxin absorption and j Nausea, vomiting, abdominal pain
neutralizing circulating toxin j Less common
j Symptomatic management – Conjuctival suffusion
• Patient is admitted and isolated in a dark, quiet room – Photophobia
to prevent stimuli such as bright light, noise and – Carditis
touch that can precipitate spasm. – Meningism
• Human Tetanus Immunoglobulin (TIG) 3000– – Erythematous maculopapular rash on skin and
6000 units IM is recommended to give immediately. mucosa
TIG has no effect on toxin which is already fixed j Followed by apparent recovery
to neural tissue but it can neutralize circulating
• Second Immune Phase
tetanospasmin. j Fever
• Penicillin is the antibiotic of choice for C. tetani. j Aseptic meningitis—hall mark
Penicillin G 200,000 units/kg body weight can j Hepatitis, hepatomegaly,
137
mebooksfree.com
j Renal—hematuria, oliguria, or anuria j 250,000 units/kg/day in 4 to 5 divided doses i.v ×

j Renal failure 7 day
Icteric Leptospirosis (Weil’s Syndrome) • Alternative agents
j Cefotaxime, ceftriaxone
• Liver dysfunction • Vascular dysfunction • For penicillin allergy
j Jaundice j Hemorrhage j Children under 8 years
j Hepatomegaly j cardiovascular – Erythromycin, Amoxycillin, Ofloxacin
j Right upper quad- collapse j Children beyond 8 years
rant tenderness • Death – Tetracycline 10 to 20 mg/kg/day in 3 divided
• Kidney j Due to renal failure
doses
j Uremia j Hepatic failure
Or
j Oliguria j Cardiopulmonary
– Doxycycline 100 mg twice for 5 days
j Anuria failure
Outcome
j Kidney failure j Hemorrhage
• Self-limited
Laboratory Diagnosis • Relapse may occur
• Dark Field Microscopy (DFM) Prevention
j Leptospires in blood and CSF within first 10 days • Avoid contaminated water and soil
j In urine from the 2nd week • Rodent control
• Detection of Antibodies • Good sanitation
j Macroscopic slide agglutination test (MSAT)
– Genus specific test 10.4.8 Tuberculosis (TB)
– Killed leptospira used as antigen
j IgM-ELISA and Dipstick test Epidemiology
– Detect genus specific IgM antibodies—around • Tuberculosis (TB) is the largest killer among
4th day of illness infectious diseases in children
– Do not differentiate between pathogenic and • About one-third of the world population is believed
saprophytic leptospira to be infected with tuberculous bacteria
– Infecting serovar not identified • >95% of the cases occur in the developing world
j Microscopic agglutination test (MAT) • Annual risk of TB in children: 2%–5%
– Gold standard • Prevalence in under 5 years population is 2.8%
– Serovar specific test • Sixfold increase in HIV infection
– High specificity Causative agent
– Positive 10 to 12 days after symptom onset • All pulmonary TB-Mycobacterium tuberculosis
– titer 1:80 or four fold increase in 2 weeks • Extrapulmonary
apart—diagnostic j Mostly due to M. tuberculosis
• PCR assay j Very rarely Mycobacterium bovis can be the cause
• Others • M. tuberculosis
j CBC—leukocytosis j Acid fast bacilli
j ESR is elevated j Obligatory aerobic
j Liver function test Transmission
– Serum bilirubin increased
• Respiratory route
– Liver enzymes elevated j From open case
j Serum creatine kinase—elevated j Via droplet nuclei
CSF
j
• Rarely by
– Moderate pleocytosis (<500/µL) j Ingestion of infected material
– Predominantly mononuclear cells j Skin
– Increased protein (50–100 mg/dL) j Mucous membranes
– Normal glucose j Transplacental
Urine
j
• At risk
– Microscopic pyuria j Household contact with sputum smear positive
– Hematuria pulmonary TB
– Moderate proteinuria (++ or more) j Infections, such as measles, varicella-flares up
j Chest radiograph—pneumonitis latent TB
Treatment j Malnutrition
• Penicillin j Immunocompromised
j Drug of choice j HIV
138
mebooksfree.com
Clinical features Lymph node Genitourinary system

Upper respiratory tract Cardiovascular system • Scrofula • Flank pain
Laryngeal tuberculosis Pericarditis • Superficial regional • Hematuria
• Croupy cough, • Fever nodes • Hydronephrosis
hoarseness, and • Weight loss • Commonly cervical • Stricture
dysphagia • Pericardial friction rub group Genital TB
Middle ear • Enlarged nodes— Salpingitis
• Painless otorrhoea nontender, firm, Epididymitis/Orchitis
• Facial palsy matted
• May rupture forming
Disseminated TB Gastrointestinal system
draining sinus
Multiple organs involved • Hematogenous spread
Bone/Joint
Miliary TB • Swallowing infected
Potts disease spine
• Hematogenous sputum
Tuberculous arthritis/
spread Tuberculous peritonitis
osteomyelitis
• Disease in two or • Abdominal pain
more organs • Abdominal distension
• High-grade/low-grade • Doughy abdomen
fever • Rolled-up omentum Investigations
• Weight loss • Irregular abdominal • Demonstration of organism
• Altered sensorium mass j Samples
• Cyanosis and respira- • Ascites – Sputum
tory distress Tuberculous enteritis – Nasopharyngeal aspirate after nebulization
• Lymphadenopathy • Vomiting with salbutamol and hypertonic saline
• Hepatosplenomegaly • Chronic diarrhea – Gastric lavage on two consecutive days after
Meningitis • Constipation overnight fasting
Choroid Tubercles • Malabsoprtion – BAL
Mesenteric adenitis – Pleural fluid
Lower respiratory tract Central nervous system – CSF
Primary complex Lymphohematogenous j Specimen is prepared with Ziehl–Neelson (ZN)
• Fever spread stain
• Weight loss Meningoencephalitis j Cultured on Lowenstein–Jenson medium;
• Evening rise of Stage 1 7–10 weeks of incubation
temperature • Fever, headache, j Radiometric methods
• Night sweats irritability
– BACTEC radiometric assay
• Loss of appetite Stage2
– Septi-chek AFB system
• Dry cough • Meningeal signs
– Mycobacterial growth indicator tube (MGIT)
• Localized • Cranial neuropathy
wheeze +/− • Hypertonia system
Progressive primary • Focal neurological • Host’s response: Tuberculin test
disease deficits (Mantoux test)
• High grade fever Stage3 j Detects delayed hypersensitivity to specific
• Productive cough • Coma antigenic components of MTB which develops
• Lung signs-decreased • Decerebrate/ 4–6 weeks after infection
air entry decorticate posturing j Read after 48–72 h
• Crepitations • Death j Interpretation: Size of induration
Pleural effusion Tuberculoma – <5 mm: Negative
• In children more than • Fever, headache, – >10 mm: Positive
5–6 years age seizures – 5–10 mm: Borderline; may be considered
• Fever • Focal signs positive in immunocompromised
• Breathing difficulty • Ring-like lesion on • Radiological investigations
• Pleuritic chest contrast CT brain j Chest X-ray
pain—pain on deep j CT scan
inspiration j Contrast enhanced MRI—for CNS
• Pleuritic rub
• FNAC and histopathology of lymph nodes and other
• Stony dull percussion
tissues
• Decreased air
entry
• Cartridge-based nucleic acid amplification test
(CB NAAT)
139
mebooksfree.com
Diagnostic algorithm
Treatment of TB: WHO category • As per latest guidelines (2017), daily regimen with
a fixed dose combination of ATT as per appropriate
TB treatment regimens weight bands is preferred than intermittent
Treat- Con- regimen.
ment cat- Intensive tinuation Drug Dosage for Pediatric TB
egories Type of patients phase phase
Inj.
New • New sputum 2 HRZE 4 HRE
Number of tablets Strepto-
cases smear-posi-
(dispersible FDCs) mycin
tive PTB
• New smear Continua-
negative PTB Intensive phase tion phase
• New extrapul-
monary TB Weight HRZ E HRE
(EPTB) category
(kg) 50/75/150 100 50/75/100 mg
Previous- • Recurrent TB 2 5 HRE
ly treated case HRZES + 1 4–7 1 1 1 100
cases • Treatment HRZE 8–11 2 2 2 150
after failure
12–15 3 3 3 200
• Treatment
after loss to 16–24 4 4 4 300
follow up 25–29 3 + 1A 3 3 + 1A 400
• Retreatment 30–39 2 + 2A 2 2 + 2A 500
others
A = Adult FDC (HRZE = 75/150/400/275; HRE = 75/150/275)
140
mebooksfree.com
• Intensive phase can be given for 1 month more • Treatment failure: Biological specimen is positive by
j If there is poor/no response to Rx after 8 weeks smear or culture at the end of ATT
• Continuation phase can be given for an additional • Failure to respond: Biological specimen is positive by
3–6 months: smear or culture at 12 weeks of compliant intensive
j In children with TBM phase (for pediatric TB patients)
j Miliary/disseminated TB • Lost to follow-up: Treatment was interrupted for 1
j Osteoarticular/spinal TB consecutive month or more
Indication for steroids • Not evaluated: No treatment outcome is assigned
• CNS TB • Treatment regimen changed: Regimen changed due
• Endobronchial TB to multidrug resistant TB. Previously, it was called as
• Miliary TB ‘switched over to MDR treatment’
• Pericardial effusion Preventive therapy
Case definitions: • Indications
• Microbiologically confirmed TB case refers to a j All asymptomatic contacts less than 6 years
presumptive TB patient with biological specimen (after ruling out active disease)
positive for AFB stain or culture, or molecular j All HIV infected children with contact history or
testing. tuberculin positivity
• Clinically diagnosed TB case refers to a presumptive j All tuberculin positivity receiving
TB patient who is not microbiologically confirmed, immunosuppressive therapy
but has been diagnosed with active TB by a clinician j Child born to mother with active TB (after ruling
on the basis of X-ray abnormalities, histopathology, out congenital TB)
or clinical signs with a decision to treat with full • Regimen:
course of ATT. j INH 10 mg/kg daily for 6 months
• Smear positive: Any sample (sputum, induced
sputum, gastric lavage, bronchoalveolar lavage)
positive for acid-fast bacilli.
• New case: A patient who has had no previous ATT or 10.5 Viral infections
for less than 4 weeks.
• Previously treated patients have received 1 month or 10.5.1 Infectious mononucleosis
more ATD in the past. This is further classified into:
j Recurrent TB case: Patient declared cured/ • Infection caused by Epstein–Barr virus (EBV)
completed therapy in past and has evidence of Pathophysiology
recurrence. Previously called ’relapse’ • Transmission of EBV
j Treatment after failure: A case of pediatric TB who j By saliva from asymptomatic carriers and
fails to have bacteriological conversion to negative patients
status or fails to respond clinically or at the end of j Adolescents—through sexual activity
most recent treatment. j Blood transfusion and organ transplantation
• Treatment after loss to follow-up: A patient who has • Elicits humoral and cellular response to the virus
taken treatment for at least 4 weeks and comes after • Efficient T-cell response-control of the primary EBV
interruption of treatment for at least 1 month and has infection and lifelong suppression of EBV
microbiologically confirmed disease. • Ineffective T-cell response-uncontrolled B-cell
• Others: Cases who are smear negative or extra proliferation, resulting in B-lymphocyte
pulmonary but considered to have relapse, failure to malignancies,
respond or treatment after default or any other case
Clinical findings
which do not fit the above definitions.
• Incubation period : 4–8 weeks
Clinical follow-up • Prodromal symptoms include fever, sore throat,
• Should be at least once every month malaise, anorexia
• To observe improvement of symptoms, weight gain, • Lymphadenopathy
control the comorbid conditions, and to monitor side j Firm and tender
effects of ATT j Anterior cervical and Posterior cervical nodes
Treatment outcomes • Throat
• Cured: A microbiologically confirmed TB who j Exudative or nonexudative pharyngitis
becomes smear or culture negative at the end of ATT j Tonsillitis with/ without airway obstruction
• Treatment success: TB patients either cured or j Palatal petechiae
‘treatment completed’ j Uvular edema
141
mebooksfree.com
• Rash • Characterized by fever, coryza, palpebral conjunctival

j Macular, scarlatiniform, or urticarial rash injection and moribilliform rash
j In patients taking penicillin or ampicillin Etiopathogenesis
• Periorbital edema • Caused by measles virus (RNA virus)
• Splenomegaly (50%–75%) j Genus: Moribilli virus
• Tender hepatomegaly (30%) j Family: Paramyxoviridae
Complications j Only 1 serotype
• Secondary attack rate very high (>90%) in susceptible
• Splenic rupture • Neurological cases
• Acalculous syndromes
cholecystitis • Aseptic meningitis,
• Cases are infectious 3 days before to 4–6 days after
onset of rash
• Mesenteric Adenitis encephalitis,
• Pancreatitis, meningoencephalitis • Portal of entry
Myocarditis, • Bell’s palsy j Respiratory tract/conjunctiva
pericarditis • Guillain–Barré j Contact with large/small droplet aerosol
• Myositis, Glomerulo- syndrome Pathogenesis
nephritis • Virus → migrates to regional lymph nodes → primary
viremia → reticulo-endothelial system → secondary
Laboratory Evaluation viremia → body infection
• CBC • Hyperplasia of lymphoid tissue especially with
j Lymphocytosis Multinucleate giant cells with intra nuclear and
j Atypical lymphocytes intracytoplasmic inclusions—Warthin–Finkeldey
j Relative atypical lymphocyte count—equal to/ Reticuloendothelial giant cells
greater than 20% • Incubation period: 8–12 days
• ESR Clinical features
j Elevated transaminases • Begins with secondary viremia
• Serological testing for heterophile antibodies • High fever, dry cough, coryza, conjunctivitis
j Paul Bunnell test—sheep RBCs agglutinate in • Koplik’s spots—Seen 2 days after the onset of fever
presence of heterophile antibodies j Tiny white raised spots on the reddish buccal
j Monospot test—agglutination of horse RBCs in mucosa opposite the second molars
presence of heterophile antibodies j Pathognomonic of measles
• IgM and IgG antibodies directed against the Viral • Typical morbilliform rash (Fig. 10.3)—Seen 4 days
Capsid Antigen (VCA) after onset of fever
j IgM VCA—confirms diagnosis j Starts behind the ears, then spreads to face, trunk,
j IgM and IgG VCA—differentiates acute from extremities, palms and soles
previous infection j Confluent rash that desquamates in a week
• Antibodies against Early antigen and Epstein Barr j Fades in about 7 days leaving brawny desquamation
Virus Nuclear Antigen • Fever peaks with the rash and falls 2–3 days later
Management Complications
• Acute infection
j Rest Respiratory CNS GIT-
j Avoid contact sports in first 3 weeks of illness due • Otitis media • Aseptic men- • Persistent
to risk of splenic rupture • Laryngotracheo- ingitis diarrhoea
j Symptomatic treatment bronchitis • Encephalitis • Hepatitis
For complications—Short course of • Pneumonia • Guillain
j
Others
corticosteroids < 2 weeks • Interstitial Barre
• Noma of
pneumonia syndrome
• Chronic active disease Cheek
(giant cell pneu- • Hemiplegia
j Antivirals—Acyclovir, valacyclovir, penciclovir, • Gangrene
monia) • Retrobulbar
ganciclovir, and foscarnet secondary
• Bronchiectasis neuritis
Prognosis to purpura
• Flaring of TB • Subacute
Excellent in absence of complications fulminans/
sclerosing pa-
DIC
nencephalitis
10.5.2 Measles
Lab investigations/diagnosis
• Acute viral exanthematous illness • CBC
142
mebooksfree.com
• Indications
j Susceptible household contacts of measles
j Infants < 6 months
j Pregnant women
j Immunocompromised children
Prognosis and outcome
• Case fatality 1–3/1000
• Death due to pneumonia/secondary bacterial infection
• Modified measles—Milder and shorter and in
partially immune persons
• Hemorrhagic measles: Purpuric rash and bleeding
from nose, mouth and GIT
10.5.3 Mumps
Figure 10.3 Morbilliform rash of measles. • Self-limiting acute Viral illness caused by Mumps
virus characterized by fever and unilateral or bilateral
j Lymphopenia parotid swelling
j Leukocytopenia Aetiology
j Absolute neutropenia • Mumps virus—Single stranded RNA virus, belongs to
• Smear of nasal mucosa—multinucleate giant cells family paramyxoviridae
• Measles IgM antibody • Only one immunotype
• Measles IgG Antibody • Humans are the only natural host
j 4-fold rise between acute and convalescent Pathogenesis
sera. • Spreads from person to person by droplet infection
j 1st sample on 7th day after the onset of the • Virus enters through nose or mouth → Multiplies in the
rash parotid gland and respiratory epithelium → Viremia →
j 2nd sample 10–14 days later to confirm Localizes in the glandular and nervous tissue
• Isolation by tissue culture in human embryonic or • Present in saliva one week before and after onset of
rhesus monkey kidney cells parotid swelling
j Cytopathic diagnosis in 5–10 days • Maximum infectivity 1–2 days before and 5 days after
j Multinucleate giant cells, intranuclear parotid swelling
inclusions
Clinical features
• Viral genotyping in a reference laboratory
• Incubation period: 16–18 days
• CSF analysis in encephalitis
j Increased lymphocytes, proteins,
• Initial symptoms include fever, headache, malaise and
ear ache that increases on chewing
Glucose normal
• Swelling starts in one parotid gland initially and
j
Treatment can progress to involve the other side. Pain over the
• No specific antiviral parotid area that increases on tasting sour food
j Ribavirin (experimental) • Swelling obliterates the angle of the jaw and lifts ear
• Entirely supportive therapy lobule upward and outward (Fig. 10.4)
j Antipyretic for fever • Other glands that can be involved
j Bed rest j Submaxillary—Swelling beneath the mandible
j Adequate fluids j Sublingual-Swelling in the submental area and on
• Treatment of complications—e.g., Antibiotics if floor of the mouth
bronchopneumonia or otitis media
Complications
• Vitamin A supplementation
Prevention • Epididymo-orchitis • Pneumonia
• Oophoritis • Thyroiditis
• Measles/MMR vaccine-9 months
• Meningo-Encephalitis • Arthritis
• MMR vaccine—15 months and 4–6 years
(Most common) • Deafness-, uni-, or
Post Exposure Prophylaxis • Pancreatitis bilateral
• Vaccine within 72 h of exposure • Myocarditis • Eyes- Bilateral
• Immunoglobulin upto 6 days of exposure Dacryoadenitis, Optic
j 0.25 mL/kg Neuritis
j 0.5 mL/kg—immunocompromised children
143
mebooksfree.com
• After an acute episode, virus persists for years in

sensory nerve ganglia
• Reactivation can occur many years later leading on to
herpes zoster/Shingles
Pathogenesis
• Spread by respiratory/direct contact with the lesion
fluid
• Virus infects upper respiratory tract mucosa/conjunctiva
• Replicates in regional lymph nodes
• Primary viremia
• Spreads to various organs
• Secondary viremia
• Spreads toxin
Clinical features
• Any age—maximum between 5–9 years
• Incubation period—14–16 days
• Fever, malaise and headache
• Rash on the 1st day of fever
j Pruritic
j Occurs in crops over 3–4 days
j Pleomorphic: papule- tear drop vesicle-pustule-scab
j Clouding and umbilication of vesicle in 24–48 h
j Centripetal distribution
j Involves oral mucosa, conjunctiva and vagina
j Scarring if secondary infection
Figure 10.4 Right parotid swelling in mumps (Black arrow) Other types
• Progressive varicella
Investigations • Hemorrhagic varicella-Hemorrhagic rash with
• Leukopenia, lymphocytosis thromboctopenia
• Serum amylase is elevated but serum lipase normal • Congenital varicella if mothers have active infection
• Complement fixation antibody titers • Varicella embryopathy–Congenital varicella syndrome
j Antibodies to the ‘S’ antigen-rise in 1st week of j Eye—Cataract
illness j Skin—Scarring (cicatrix) and limb hypoplasia
j V antigen -several weeks later j Brain—Microcephaly
• Neutralizing and hemagglutination inhibiting j Lungs—Pneumonia
antibodies during convalescence • Neonatal varicella
• Isolation from saliva, CSF, blood • Varicella gangrenosa—gangrenous ulceration of the
Treatment skin and subcutaneous tissues
• Supportive • Varicella bullosa—Lesions are bullous instead of
vesicles
• Antipyretic and analgesic
• Bed rest • Breakthrough varicella following varicella vaccination
• Testicular support for orchitis Complications
Prognosis • Secondary infection- impetigo, necrotizing fascitis
• Bacterial Sepsis
• Excellent • DIVC
Prevention
• Pneumonia
• MMR vaccine given at 15–18 months • CNS—post infectious encephalitis, GBS, Transverse
myelitis, cerebellitis
• Cardiac—myocarditis, pericarditis, endocarditis
10.5.4 Varicella • Renal—Glomerulonephritis
• Highly contagious acute febrile infection • Others—hepatitis, arthritis, osteomyelitis, purpura
Etiology fulminans
• Caused by varicella zoster virus • Reye’s syndrome
• DNA virus belonging to Herpes virus family • Reactivation of latent virus even years later—Herpes
• Primary infection causes varicella/chicken pox zoster
144
mebooksfree.com
Diagnosis – Breast milk lipase destroys virus; breast milk

• Clinical may be given after storing
• Virus isolation from vesicle fluid • Blood and blood product transfusion 3%–6%
• Electron microscopy/immunofluorescent staining • Sexual abuse
• Serology—latex agglutination, indirect fluorescent • drug abuse and tattooing
antibody and enzyme immunoassay Factors that increase risk of vertical transmission
Treatment • Low maternal CD4 count <700/cumm or CD4+/
• Supportive CD8+ <0.6
j Antipyretics—Paracetamol • High viral load in mother
j Aspirin avoided as it causes reye’s syndrome • Maternal seroconversion just before delivery
j Antihistamine for itching • Anemia
j Calamine for soothing • Vitamin A deficiency in mother
j Eye care • Cervico vaginal infections
j Mouth care • PROM >4 h
• Antibiotics for secondary infection • Vaginal delivery
• Antiviral: Acyclovir therapy • Preterm (<34 weeks)
j In immune compromised • Low Birth Weight
j Within 72 h of rash • Zidovudine and Caesarean section reduce risk of
– 20 mg/kg/dose 4 times a day × 5 days transmission by 87% if viral load is high
– Maximum dose: 800 mg • If viral load is <1000 copies/mL Caesarean section is
j Disseminated infection not effective
– IV acyclovir 10 mg/kg/dose 8 hourly × 7 days Pathogenesis
Prevention • Infects cells in the immune system
• Isolate the patient • Three steps in viral entry
• Vaccination j Binding of GP 120 to CD4 molecule on the host
j 12 months to 13 years: Single dose of varicella vaccine j Binding to a coreceptor (CCR5/CXCR4) on the cell
• Post exposure prophylaxis (Varicella Zoster surface exposing GP 41
immunoglobin—VZIG) j Viral and cell membrane fuse
j Immunodeficiency/immunosuppressive drugs
j Newborn with mother having varicella within
5 days before and 2 days after delivery
j Household contact within 72 h
• Common cause of death in children is encephalitis
10.5.5 HIV in children

Etiology
• Caused by HIV 1 virus
• Retroviridae family
• Lentivirus genus
• Single stranded RNA virus
Modes of transmission in children
• Vertical transmission >90%
j Intrauterine transmission
– Lab evidence of infection seen in the 1st week
– Become symptomatic within a few months or
in the 1st year
j Intrapartum
– Exposure to infected blood and secretions in
birth canal
j Breast feeding
– Increases the risk by 14% if infection is
acquired prenatally and by 29% if infection is
acquired postnatally
– WHO recommends breast feeding in
developing countries
145
mebooksfree.com
Disease patterns j Hepatosplenomegaly

• Rapid progression (20%) j Parotitis
j Symptoms in the 1st year j Dermatitis
j Die within 2 years j Recurrent upper resp. infection / sinusitis
• Slow progression (60%–80%) • B—Moderately symptomatic
j Become symptomatic after 2 years j Hematological abnormalities
j Median survival time 6 years j Recurrent bacterial pneumonias, meningitis
• Long term survivors (5%) j Oesophageal thrush
j No progression for about 8 years j Disseminated varicella
j Normal CD4 count j Fungal infections
Clinical features • C—Severely symptomatic
• Rapid progression j Serious bacterial infections
j Chronic/persistent/recurrent diarrhea j Extrapulmonary disseminated cryptococcosis
j Failure to thrive j Kaposi’s sarcoma
j Developmental Delay j Lymphoma
j Oral thrush • Opportunistic Illnesses in HIV Infection
j Hepatosplenomegaly j Multiple or recurrent bacterial infections
j Encephalopathy j Candidiasis of bronchi, trachea, lungs,
j PCP seen at 10–14 weeks of age esophagus
• Slow progression j Coccidioidomycosis, disseminated or
j Chronic/persistent/recurrent diarrhea extrapulmonary
j Chronic / recurrent oral thrush j Cryptococcosis, Histoplasmosis, Isosporiasis
j Anemia, neutropenia, thrombocytopenia j Cytomegalovirus disease
j Nephropathy j Kaposi sarcoma, Lymphoma
j Cardiomyopathy j Mycobacterium tuberculosis or atypical
j Recurrent Herpes zoster infections mycobacterial infection
• AIDS defining infections j Pneumocystis jiroveci pneumonia
j Opportunistic infections (Pneumocystis jerovici j Recurrent Pneumonia
infection) j Progressive multifocal leukoencephalopathy
j Oesophageal, tracheal, bronchial candidiasis j Salmonella septicemia, recurrent
j Disseminated mycobacterium avium j Toxoplasmosis of brain, onset at
complex age >1 month
j Disseminated extrapulmonary TB j Wasting syndrome
j Chronic intestinal cryptosporidium Diagnosis
j Disseminated extra pulmonary cryptococcosis, • Virological tests in children < 18 months of age
histoplasmosis, coccidoidomycosis j HIV DNA PCR
j Cerebral toxoplasmosis j HIV RNA PCR
j Recurrent bacterial pneumonia • Virus culture
j Salmonella bacteremia j 2 tests have to be +ve at one month interval
j HIV encephalopathy • Serological tests in children > 18 months of age
j Wasting syndrome j ELISA/Western Blot
j Progressive multifocal leucoencephalopathy • In asymptomatic children 3 tests have to be done and
j Lymphoma in symptomatic 2 tests have to be done
j Kaposi’s sarcoma • Routine investigations
• Additional AIDS defining infections j HB
j In children < 13 years of age j Urine RE / culture
– Recurrent serious bacterial infections j Mx > 5mm with 5 TU
– Lymphocytic interstitial pneumonia j ALT
j In children > 13 years j Creatinine
– Invasive cervical cancer j CD4 count
– Pulmonary TB Treatment
– CD 4 count < 14% or < 200/µL • General Care
Clinical categories • Immunization
• N—Asymptomatic j Routine for asymptomatic and mild
• A—Mildly symptomatic (any 2) immunosupression
j Lymphadenopathy j Additional measles vaccine at 6 months of age
146
mebooksfree.com
j Symptomatic / Moderate to severe – Voluntary counseling and testing to test AN HIV

immunosupression status
j Avoid live vaccines – Management of high risk factors
j Rotavirus and typhoid vaccines to be avoided in all – HAART when indicated for the mother
categories - Tenofovir (TDF) 300 mg + Lamivudine
• PCP prophylaxis for all exposed children till proved (3TC) 300 mg + Efavirenz (EFV) 600
HIV –ve mg to mother and Single daily dose of
j (Cotrimoxazole 5 mg/kg of trimethoprim × Syrup Nevirapine (2mg/kg) for 6 weeks to
1 year) newborn
• Nutrition – If HAART is not indicated or if it is inaccessible,
• Anti-retroviral therapy (ART) follow WHO recommendations
j Nucleoside/Nucleotide reverse transcriptase - Zidovudine from 28 weeks of pregnancy
inhibitors—Zidovudine - Onset of labor Zidovudine + lamivudine + single
j Non nucleoside reverse transcriptase inhibitors— dose of nevirapine
Nevirapine - After delivery Zidovudine + lamivudine ×
j Protease inhibitors—Lopinavir 1 week
j Fusion inhibitors—enfuvirtide – New born
j Integrase inhibitors—MK-0518 - Single dose of Nevirapine within 72 h
j CCR5 coreceptor inhibitor—Maroviroc +Zidovudine × 1 week
j Highly active antiretroviral treatment (HAART) • For HIV positive women presenting directly in
leads to labour
– Complete suppression of plasma viraemia j Immediate Maternal ART (Tenofovir + Lamivudine
– Reduces the frequency of opportunistic + Efavirenz)
infections j For infant: Daily Nevirapine syrup for 6–12
– Improves quality of life weeks
• When to start ART
j Infants
– All infected children/Symptomatic infants or if 10.5.6 Dengue
the CD4 count is < 25%
j After infancy • Acute viral infection caused by dengue virus
– Clinical symptoms or severe immunodeficiency • Dengue virus—ss RNA virus belongs to flaviviridae
family
(CD4 < 15%)
j High viral load (>100,000 copies / mL) • Four serotypes
DEN-1, DEN-2, DEN-3, DEN-4
•
j
WHO guidelines to be followed
j Type 2 is most common in India
j Triple drug therapy advocated
j NACO—Zidovudine + Nevirapine + Mode of Transmission
Efavirenz • Transmitted by bite of infected female Aedes aegypti
• Prevention of Parent to child transmission mosquitoes and Aedes albopictus
(PTCT) • Mosquitoes remain infective for life
j Education • Human beings are amplifying hosts
j Take precautions while using blood/blood Aetiopathogenesis
products First infection
j Screening blood/blood products • Homologous and heterologous neutralizing
j Use sterile injection equipment antibodies
j No sharing of needles by drug users • Self-limiting febrile illness
j Antenatal mothers
147
mebooksfree.com
Second infection
WHO Classification of dengue
148
mebooksfree.com
Older classification • Dengue hemorrhagic fever and shock syndrome

• Classical dengue j Three classical stages are described (Febrile, leaky
• Dengue hemorrhagic fever and congestive)
j Fever 2–7 days j Characterized by Bleeding manifestations,
j Minor/major bleeding capillary leak features and hypotension.
j Thrombocytopenia— < 1 lakh/µL Cold peripheries, tachycardia, thread pulse,
j Increased capillary permeability reduced blood pressure, reduced urine output
– Hematocrit increased 20% or more or and metabolic acidosis suggests poor tissue
– Pleural effusion (CXR) or perfusion
– Ascites (USG) or j Can progress to multiorgan dysfunction
– Hypoalbuminemia • Atypical manifestations
• Dengue shock syndrome j Seizures
j Above criteria as for DHF j Encephalopathy
j PLUS j Paresis
j Tachycardia j Respiratory distress
j Hypotension j Liver failure
j Narrow pulse pressure <20 mm of Hg j CCF
j Poor perfusion Complications
Risk factors for severe dengue • Fluid loss
• Second infection • Hypervolemia from overhydration
• Dengue virus 2 • Electrolyte loss
• Viral genotype, mutant etc • Febrile seizures
• Younger age • Bradycardia
• Hyperendemicity • Arrhythmias–Ventricular extrasystole
Clinical Features of dengue Differential diagnosis
• Incubation period: 1–7days • Malaria
• Febrile phase is characterized by acute Onset, high • Typhoid
grade fever lasting for 2-7 Days. Associated features • Leptospirosis
include facial flushing, erythema, generalized myalgia • Meningococcemia
(Back-Break Fever), headache, retro-orbital pain and • Rickettsial fever
arthralgia. Fever is often biphasic. Diagnosis
• Transient macular rash appears during first 24–48 h • Antibody detection
that blanches on pressure. Rash is maculopapular/ j Hemagglutination Inhibition (HAI)
moribilliform, spares palms and soles. Rash usually j ELISA (IgG/IgM)
lasts for 1–5 days and resolves with desquamation. j Rapid test (IgG/IgM)
• Minor Hemorrhagic manifestations and hepatomegaly • Antigen detection
• Critical phase is seen 3–7 days after onset of fever. j NS1 and E/M antigen
Severe dengue with bleeding/shock/organ dysfunction j RNA detection
is seen during this phase. j PCR
• Recovery phase follows 24–48 h after critical phase. • Viral isolation
• Severe dengue: Fever for > 2 days + any one of the • Other tests
following: j ECG
j Evidence of plasma leakage: Pleural effusion, – Sinus bradycardia
Ascites, ↑ Hematocrit – Prolonged PR interval
j Circulatory failure—Cold clammy extremities, – Flat T wave
hypotension
• Dengue hemorrhagic fever/DSS
j Spontaneous bleeding j Hemoglobin
j Altered consciousness, Lethargy, Coma, Convulsions j Hematocrit—Hemoconcentration > 20%
j Persistent vomiting j CBC
j ↑ abdominal pain with tenderness in right – Neutropenia
hypochondrium – Thrombocytopenia
j Jaundice j Bleeding time prolonged
• Severe dengue thus includes j Prothrombin time-prolonged
j Dengue hemorrhagic fever j Fibrinogen reduced
j Dengue shock syndrome j FDP-increased
j Encephalopathy j USG-ascites, GB wall edema
149
mebooksfree.com
j Positive Hess capillary fragility test Supportive therapy

j Imaging—CXR, USG for pleural effusion, Ascites • Colloid transfusion
Treatment • Platelet transfusion—
• Dengue without warning signs j If clinically significant bleeding present
j Symptomatic j In asymptomatic cases if platelet counts are less
– Paracetamol than 20,000/cubic mm
– Plenty of oral fluids • FFP transfusion
– Avoid salicylates and other nonsteroidal j Refractory shock
antiinflammatory drugs j To replenish clotting factors
• Treatment of severe dengue DHF • Inotropes—Dopamine, Noradrenaline, Adrenaline
j Start 2 intravenous lines Prognosis and outcome
j The basic principle is volume replacement • Dengue fever is usually self-limiting and benign.
j Send investigations • In dengue hemorrhagic fever, mortality is 40% to
– Blood grouping typing, cross matching 50%.
– Hemoglobin • Death due to shock, bleeding and overhydration
– PCV Prevention
– Platelet • Elimination of adult mosquitoes and larvae
• Spraying or fogging with malathion
• Avoid stagnation of water especially after rainy
season
• Vaccines under development
10.6 Malaria
• Major public health problem in India

• Acute and chronic illness
• Characterized by
j Fever with chills and sweats
j Anemia
j Splenomegaly
Etiology
• Malarial parasites
j Plasmodium Falciparum
j P. Vivax
j P. Malariae
j P. Ovale
j P. Knowlesi (recent addition)
j Treatment of severe dengue DSS
150
mebooksfree.com
• Transmission • Immune evasion

j Bite of female Anopheles Mosquitoes j Intra cellular replication
j Others routes of transmission are blood j Vascular cyto adherence
transfusion, contaminated needles and vertical j Antigen variation
transmission j Impaired Ab synthesis
Pathophysiology
Clinical features • Disseminated intravascular coagulation

• Asymptomatic during initial phase • Pulmonary edema
• Incubation period • Acute kidney injury
j P. falciparum: 9–14 Days Cerebral Malaria
P. vivax: 12–17 Days
j
• Life threatening complication of falciparum malaria
P. ovale: 16–18 Days
j
• Characterized by gradual onset of irritability and
j P. malariae: 18–40 Days listlessness progressing to convulsions, altered
• Paroxysms of fever with paroxysms of fatigue is mentation and coma. Rapid progression to coma
classical for malaria within 1–2 days, which cannot be explained by
j High grade intermittent fever with chills, rigor and hypoglycemia or a transient postictal state and
sweating absence of other causative disease in a child
j Fever pattern— with falciparum malaria. Diffuse symmetric
– Quotidian (Peaking every 24 h) —Seen in P. encephalopathy is characteristic. Focal findings
falciparum are extremely rare and should point towards an
– Tertian (Peaking every 48 h) —P.vivax alternative diagnosis. Frank signs of meningeal
– Quartan (Peaking every 72 h) —P. malariae irritation are rare. Tendon reflexes and muscle tone
– No specific pattern in falciparum are highly variable.
• Fever is often accompanied by prodromal features like • Features suggestive of fever, vomiting, cough and
headache, lethargy, nausea, vomiting, musculoskeletal diarrhea may be present.
pain and rarely diarrhea.
• Jaundice, hepatosplenomegaly and shock like state
• Classical signs on examination include pallor, • Associated complications include retinal hemorrhages
jaundice and hepatosplenomegaly (15%) and DIC (5%).
Features of Severe malaria • Responds well to antimalarial therapy. Convulsions
• Cerebral malaria—Coma, convulsions are treated with diazepam/midazolam
• Severe shock like state (Algid malaria) • Associated with high mortality rate if untreated
• Hemoglobinuria (Black water fever) (20%). Approximately 10% of survivors have
• Poor feeding neurological deficit.
151
mebooksfree.com
Diagnosis
Drug sensitivity Recommended treatment
• Peripheral Smear- both thick and thin smear—Gold
standard for diagnosis Severe and Com- • Quinine + Tetracycline or
j Thick smear is used to identify malarial plicated Malaria Doxycycline or Clindamycin
parasites for 7 days
j Thin smear is used for species identification (OR)
• Rapid Diagnostic Test • Artesunate + Tetracycline or
j Parasite lactate dehydrogenase Doxycycline or Clindamycin
j Histidine rich protein—2 (HRP-2) for 7 days
• Quantitative Buffy Coat Technique (OR)
• Artemether + Tetracycline or
• Molecular Probes
Doxycycline or Clindamycin
• PCR Assay
for 7 days
• Serology
j Indirect Fluorescent antibody test (IFAT)
j Indirect Hemagglutination antibody • Chloroquine (Total dose 25 mg base/kg)—10 mg
(IHA) test base/kg stat followed by 5 mg/kg at 6, 24, and 48 h.
j Enzyme-linked immunosorbent assay (ELISA) Should be given in empty stomach and during a
Treatment febrile period.
Supportive treatment • Artesunate—4 mg/kg of body weight once daily for
• ABC 3 days
• Oxygen/Respiratory Support • SP as 25 mg/kg of sulfadoxine and 1.25 mg/kg of
• Fluid Resuscitation pyrimethamine
• Hypoglycemia correction • Mefloquine—25 mg/kg of body weight in two
• Antipyretics (15 + 10) divided doses
• Blood Transfusion • Quinine—10 mg salt/kg/dose 3 times daily for
• Diazepam/Midazolam For Seizures 7 days.
Artemisinin Combination Therapy • Tetracycline (above 8 years) 4 mg/kg/dose 4 times
• Simultaneous administration of artemisinin along daily for 7 days
with another antimalarial drug • Doxycycline (above 8 years) 3.5 mg/kg once a day for
j Reduces emergence of resistant strains 7 days
j Increases efficacy • Clindamycin—20 mg/kg/day in 2 divided doses for
7 days
• Artesunate—2.4 mg/kg IV then at 12 and 24 h and
Recommended Treatment once a day for 7 days
Drug sensitivity Recommended treatment
• Artemether—3.2 mg/kg (loading dose) IM
• Primaquine—0.25mg/kg once daily for 14 days (For
Uncomplicated • Chloroquine radical cure in Vivax malaria); 0.75mg/kg single dose
P. vivax and P. for gametocytocidal action in Falciparum malaria
falciparum—
Chloroquine
sensitive
Uncomplicated • Artesunate for 3 days + Single 10.7 Vaccines
P. falciparum— dose of sulfadoxine and py-
Chloroquine rimethabmine on Day 1
Resistant (OR) 10.7.1 Types of vaccines
• Artesunate for 3 days + Meflo-
quine on Day 2 and 3 Live attenuated vaccine Killed vaccine
(OR) • Oral Polio Vaccine (Sabin) • Injectable Polio
• Artemether and lumefantrine • Yellow Fever Vaccine (Salk)
for 3 days • Varicella • Rabies
P. falciparum— • Quinine + Tetracycline or • Measles • Japanese
Multidrug Doxycycline or Clindamycin • Mumps encephalitis
Resistant (both for 7 days • Rubella • Cholera
Chloroquine • BCG
and sulfadoxine/ • Typhoral (mutant S. typhi
pyrimethamine) strain Ty2 1a)
152
mebooksfree.com
Toxoid Subunit vaccine Deep freezers Carriers

• Tetanus toxoid • Hepatitis B vaccine • Cab temp— −15 to • Vaccine carrier—16–20
• Diphtheria toxoid (HbSAg) −25 degree celsius vials
• Typhim-Vi (Typhoid • Districts (large) and • Out of reach sessions
Vi antigen) PHCs (small) • 4 fully frozen ice packs
• In case of power failure- • Day carriers—6–8 vials
temperature maintained • Used in field if camp in
for 18–22 h nearby place
10.7.2 Cold Chain • At PHC level- for • 2 fully frozen packs
preparing ice packs
• System of storage and transportation of vaccines at
recommended low temperature from manufacturer to Ice- lined refrigerators Ice packs
actual vaccination site (ILRs) • Water- no salt
• At districts(large) and • Water upto level
• Manufacturer—> Distributor—> Vaccine Depot—>
PHCs (small) • Discarded if leakage
Provider Site—> Consumer
• Cab temp—2–8˚C found
• Equipment in cold chain • For storage with ice • Vaccines not stored at
Walk in cold rooms Cold boxes packs or tubes subcenters—supplied on
(WIC) • Used in Peripheral centers • Arrangement (top- day of use
• At regional level • Transport of vaccines bottom)- Hep B-DPT
• Stored for 3 months • Ice packs first kept at and TT-BCG-measles-
• Serves 4–5 districts bottom and sides OPV
• DPT, DT, TT—not in direct • Dial thermometer kept-
contact with ice packs recorded twice a day
10.7.3 National Immunization schedule

Delay in immuniza-
Vaccine When to give Dose Route Site tion limits in NIS
For infants
BCG At Birth—1 year 0.05 mL- ID Lt upper arm Upto 1 year of age
1mnth
0.1 mL
Hep B At birth—24 h 0.5 mL IM Mid thigh Upto 5 years of age
OPV 0 At birth-15 days 2 drops Oral Oral Upto 5 years of age
Bivalent OPV 1, 2, 3 At 6, 10, and 14 2 drops Oral Oral
weeks
IPV At 6, 14 weeks 0.1 mL Intradermal Right deltoid
Pentavalent 1,2,3 At 6, 10, and 14 0.5 mL IM Mid thigh Upto 7 years of age
(DPT + HepB + Hib) weeks
Measles 9 months 0.5 mL SC Rt upper arm Upto 5 years of age
Vitamin A—1 With measles 1ml oral oral Upto 5 years of age
For children
Pentavalent Booster 16–24 months 0.5 mL IM Midthigh
OPV Booster 16–24 months 2 drops Oral Oral
Measles–2 as MMR 16–24 months 0.5 mL SC Rt upper arm
Vitamin A (2–9)doses 16 month-5 2 mL Oral Oral
years (every 6
months)
DPT Booster 5–6 years 0.5 mL IM Upper arm
TT 10 and 16 years 0.5 mL IM Upper arm No age limit
153
mebooksfree.com
For pregnant women

Tetanus Toxoid—1 Early pregnancy 0.5 mL IM Upper arm
Tetanus Toxoid—2 4 weeks later 0.5 mL IM Upper arm
Tetanus Toxoid— If received 2 0.5 mL IM Upper arm
Booster TT doses in a
pregnancy with
in last 3 years
*JE, Rota, Pneumococcal, IPV switch, HPV, MR
10.7.4 Bacillus Calmette Guerin Disseminated BCG infection can occur in severe
j
immunodeficiency
(BCG) Vaccine
– Can be given to baby born to HIV positive
• A suspension of live attenuated Mycobacterium mothers.
bovis—Calmette and Guerin strain to produce – Can be given with all vaccines except MMR and
immunity against TB. Measles where 4 weeks interval is needed.
• Strains and Mechanism of Action: • Contraindications
j Copenhagen (Danish1331) and Pasteur strain j Dermatological infection in the area where the
which induces cell mediated immunity (CMI) vaccine is to be administered.
• Schedule: j Children on immunosuppressant drugs / congenital
j Immediately after birth (within 72 h), if missed immunodeficiency / symptomatic AIDS.
then at 45 days of life along with other vaccines.
Catch up vaccination till 1 year.
10.7.5 Hemophilus influenzae B
j
• Storage:
j Stored at 2–8°C, diluent is normal saline, discard vaccine
after 4 h if unused
• Conjugated Vaccine
j Extremely sensitive to light and heat,
j Does not have preservative Vaccines Carrier
• Dose and route of administration: HbOC C. diphtheriae
j 0.1–0.4 million live viable bacilli)—0.1 mL or PRP-OMP N. meningitides
0.05 mL based on manufacturer intradermal (with PRP-T Tetanus toxoid
Tuberculin syringe 26/27G needle) on the convex
aspect of left shoulder at insertion of deltoid (for easy
• Diseases caused by H. influenza:
visualization and optimum lymphatic drainage), j Meningitis, Bacteremia, Pneumonia, Epiglottitis,
j Site cleaned with normal saline. Avoid antiseptics Septic arthritis
• Events following BCG vaccination • Storage: 2–8°C
• Dosage and Schedule: 0.5 mL IM, Catch up vaccination
till 5 years and for Functional/anatomical hyposplenia
3 doses if started <6 6, 10, and 14 weeks.

months of age Booster at 12–18 month
2 doses if started 6–12 4 weeks interval and 1
months of age booster
1 dose if started 12–15 Single dose and 1
months of age booster
• Efficacy: >15 months of age Single dose
80% for Miliary TB / TB Meningitis
j
j 50% for Pulmonary TB

j No protection against Leprosy/other MTB disease
• Adverse Effects: 10.7.6 Pentavalent Vaccine
j Ipsilateral axillary or cervical lymphadenopathy: • Contains five antigens – Diphtheria, pertussis,
No need for ATT. tetanus, hemophilus influenza and hepatitis B.
j BCG abscess: Surgical removal and no need for • Constituents:
ATT. j Diphtheria Toxoid 20 Lf to 30 Lf
154
mebooksfree.com
j Tetanus Toxoid 2.5 Lf to 10 Lf B. • Efficacy of the vaccine: Protection is 60%–90%

j Pertussis 4 IU for Mumps, 60%–90% for Measles, 95% for
j HBsAg (rDNA) 10 mcg Rubella
j Purified capsular HIB Polysaccharide (PRP) Conju
gated to Tetanus Toxoid (carrier protein) 10 mcg
j Thiomersal 0.005 % as preservative. 10.7.8 Rotavirus Vaccine
• Schedule: At 6, 10, and 14 weeks of life
• It’s an oral, live vaccine, Types: Human Monovalent
• Dose and Route of administration:
and Human Bovine Pentavalent
j 0.5 mL, Intramuscular in anterolateral thigh
j Booster dose not recommended in India.
RV5: Human Bovine RV1: Human
• Efficacy:
Pentavalent Monovalent
j Complete vaccine series induces protective
antibody levels in > 95% of infants • Strain—Reassortant • Strain—Live attenu-
• Adverse Effects: between Bovine strain- ated human 89-12
j Pain, redness, swelling at injection site WC23 and Human [type G1P1A(8)]
j Fever strain- G1G2G3G- • Form—Lyophilized
j Irritability for a short period of time 4P1A(8) • Store 2–8°C
• Form—Liquid Virus • Diluent—Calcium
with buffer solution Carbonate, sterile
10.7.7 Mumps Measles Rubella water, xanthan
(MMR)
• Dosage and Schedule:
• Strain: j 1ml orally, each 1- mL dose of reconstituted
Mumps—Leningrad–Zagreb, Leningrad—3, Jeryl
vaccine contains at least 106 median culture
j
Lynn
infective units of virus.
Measles—Edmonston Zagreb
j
• RV1- 2 doses: 10wks –14wks (1st dose not later than
Rubella—RA27/3
12 weeks of age)
j
• Storage: It’s a lyophilized preparation, stored 2-8 • RV5 - 3 doses: 6wks—10wks—14wks (1st dose not
and light sensitive. It reconstituted with distilled
later than 12 weeks of age)
water and should be used within 4–6 h, due to risk of
• Upper age limit:
Staphylococcal sepsis, toxic shock syndrome.
j For initiation – not more than 15 wks of age
• Schedule: 2 doses j For completion-- within 32 wks of age
At 12–15 months
j
• Adverse Effects:
Next dose 4–6 years of age or 8 weeks after 1st dose.
1.2/100,000 risk of intussusception
j
j
• Catch up vaccination: In all school aged children and • Contraindication:

adolescents, with 2 doses at 4 weeks interval. j History of Allergy
• Dose and route of administration: 0.5 mL of vaccine j History of Intussusception
subcutaneous right deltoid region. j For Latex allergy—give RV5.
• Adverse Effects:
Rubella Measles Mumps 10.7.9 Rabies vaccine

• Mild rash 5% • Mild measles • Fever 7–12 Types of rabies vaccines
• Arthralgia like illness after days
• Cell culture vaccines
• Arthritis after 7–12 days in • Febrile sei-
j Human diploid cell vaccine (HDCV)
1–3 weeks in 2%–5% zures
j Purified chick embryo cell vaccine(PCECV)
post pubertal • Thrombocyto- • Aseptic Men-
j Purified vero cell rabies vaccine(PVRV)
females penic purpura ingits
• Immune 1:30,000 • Transient j Purified Duck Embryo vaccine
thrombo- • Toxic shock Parotitis Indications
cytopenic syndrome • No evidence • Post exposure prophylaxis of animal bite cases in
purpura • Avoid in immu- of autism, category II and category III cases
1:30,000 nocompromised, IBD, GBS. • Pre exposure prophylaxis for high risk for rabies –
• Avoid pregnancy. veterinarians, handling rabies patients.
pregnancy 3 • No relationship
Dosage and Schedule: Intramuscular dose – 1 mL or
months after with GBS, SSPE,
intradermal dose – 1/5th of IMRV dose = 0.2 mL (0.1 mL
vaccination Autism
in each deltoid)
155
mebooksfree.com
• Intradermal rabies vaccine schedule • Types and Dose:

– Modified Thai Red Cross regimen- j Human rabies Immunoglobulin—20IU/Kg
0,3,7,28 j Equine Rabies Immunoglobulin—40IU/Kg
• Intramuscular rabies vaccine schedule • Half of the final dose infiltrated in and around
– Essen regimen – 0,3,7,14,28 days wound, remaining half to be given intra muscular in
• Pre exposure prophylaxis – 0, 7, 28 deltoid/ anterolateral aspect of thigh
intradermal • Side Effects:
• Re-exposure prophylaxis – 0,3 days j Tenderness
Adverse effects j Stiffness
j Low grade fever
• Pain and tenderness in injection site
Rabies immunoglobin (RIG):
• Indication: All category 3 bites, immediately
(maximum up to 7 days after bite)
Category Type of Contact Type of exposure Post exposure prophylaxis (PEP)

I • Touching/Feeding of Animals None None if history reliable
• Licks on intact skin
II • Nibbling of uncovered skin Minor Wound management
• Minor scratches or abrasions Anti-Rabies Vaccine
• Without bleeding
• Immunocompromised Wound cleaning/RIG/ Full PEP
Antibody estimation 10 days after PEP
III • Single/Multiple transdermal bites Severe Wound management
or scratches, licks on broken skin RIG and ARV
• Contamination of mucous
Membrane with saliva
10.7.10 Meningococcal Vaccine • Killed whole cell V. cholerae O1 (classical and

El Tor) and V. cholerae O139
• It is used only in certain high risk situations as j It is inexpensive oral vaccine without buffer and
enumerated below in children aged 2 years or cold chain requirements administered as 2 doses
more 2 weeks apart. Licensed in India for children above
• During disease outbreaks the age of 1 year.
• Children with terminal complement component j The vaccine is given in special circumstances like
deficiencies/functional/anatomical asplenia where there is risk of an outbreak such as during
• As an adjunct to chemoprophylaxis in close contacts pilgrimages. Protection starts 2 weeks after receipt
of patients with Meningococcal disease of the 2nd dose
• There are either bivalent (A + C) or quadrivalent (A, C,
Y, W135) and contain 50 µg of each of the individual
polysaccharides, available in lyophilized form,
reconstituted with sterile water and stored at 2 to 8°C.
10.7.12 Hepatitis B Vaccine
• In infants aged 3 months to 2 years 2 doses 3 months • In a community, perinatal transmission accounts for
apart are recommended. 30%–50% of all Hepatitis B carrier states.
• For 2 to 55 years of age, a single dose 0.5 mL SC/ IM • Plasma derived and yeast derived recombinant
is recommended. HBsAg vaccines.
j Dose—10 µg in children (0.5 mL) less than
10 years; 20 µg (1.0 mL) for older persons
10.7.11 Cholera Vaccines
j Schedule—At Birth, 1, 6 and 12 months /Birth,
• Whole Cell Vaccine – B subunit of cholera toxin 6 weeks, 6 month/0, 2, 6, and 12 month
j It is an oral vaccine (with buffer), has to be j Mode of Administration—Intramuscular in
stored at 2–8°C and is administered as 2 doses the anterolateral thigh and never in the gluteal
1 week apart. It is licensed for those aged 2 years region;
and above. j Storage—2–8˚C
156
mebooksfree.com
• Vaccination in child born to a hepatitis B positive 10.7.14 Typhoid vaccine

mother:
j The newborn must receive both the 1st dose • Inactivated (heat-phenol/acetone) whole cell,
of Hepatitis B Vaccination along with parenteral vaccines
Hepatitis B immunoglobin within 24 h j Subcutaneously administered; 0.1 mL if given
of birth. intradermally
j Two primary Doses (0.25–0.5 mL) at 4–8 weeks
interval; Booster Dose Once Every 3 years
10.7.13 Varicella vaccine j Vaccine Efficacy: 70%–80%
• This is a live, attenuated vaccine of Oka • Vi-polysaccharide typhoid vaccine
j Single intramuscular dose of 25 µg with vaccine
strain cultured in human diploid cells which is
Efficacy of 64%–72%
marketed in the lyophilized form and is to
j Safe, well tolerated with no adverse reactions
be reconstituted before use, with the diluent
j No booster response due to lack of T-Cell
provided.
immunological memory stimulation by Vi Antigen
• This vaccine can be administered at the same time
j Tetanus Toxoid Conjugate Vi-polysaccharide
with other vaccines, but should be given at different
vaccine—T-CELL Dependent with booster response;
sites and with different syringes.
Disadvantages are higher cost and cold chain
•
j
Indication:
maintenance facilities administered to children
j Children with humoral immunodeficiencies/
beyond 2 years.
chronic lung/heart disease.
Children on long term salicylates/steroids,
10.7.15 Hepatitis A vaccine
j
j Household contacts of immunocompromised

children • Dosage and Mode of Administration—2 Primary Doses
j As post-exposure prophylaxis in susceptible (720 EU in adults and 360 EU/mL in children) and
healthy non pregnant contacts preferably within • A Booster Dose after 6–12 Months administered
3 days of exposure (efficacy 90%) and potentially intramuscularly.
up to 5 days of exposure • Storage at +2 to +8 0˚C; Claimed shelf life of 3 years.
• Dosage Schedule: Single dose to be given (0.5 mL • Duration of protection in terms of anti HAV titre
minimum infectious virus of 1000 Plaque Forming of > 10 IU/L: 10 years After The Booster
Units) subcutaneously in the arm of children
<13 years; 2 doses at 4–6 interval in children above 10.7.16 Pneumococcal vaccine
13 years.
• Adverse effects occur in 5% of the recipients—pain, • Two types
redness, swelling, fever, vesicular rash in 3%–7% Pneumococcal conjugate vaccine (PCV):
within 6 weeks, • Minimum age 6 weeks
• Breakthrough varicella is defined as varicella • Catch-up
developing more than 42 days after immunization
6 to 12 months 2 doses 1 month apart,
and usually occurs 2–5 years following
and 1 booster
vaccination.
12 to 23 months 2 doses 2 month apart
• Varicella Zoster Immunoglobulin (VZIG)
j dose of 0.2–1.0 mL/kg diluted in normal saline 24 to 60 months Single dose
over 1 hour
j Indication: • Single dose may be administered (6 to 18 years of
j Neonates born to mothers who develop age) in children with functional/anatomical asplenia,
varicella 5 days before or 2 days after delivery. cochlear implant, CSF leak
j All neonates born at < 28 weeks of gestation/ with Pneumococcal polysaccharide vaccine (PPSV):
birth weight < 1000 gms, exposed in the neonatal • Minimum age 2 years
period. • Both PCV and PPSV can be used in certain high risk
j Pregnant women exposed to varicella. children group.
j If non affordable/ not available, other options
with uncertain efficacy are,
j IVIG @ 200 mg/kg or Online supplementary materials:
j Oral acyclovir 80 mg/kg/day beginning Please visit MedEnact to access chapter wise MCQs and
from the 7th day of exposure and given for previous year pediatrics theory questions asked in various
7–10 days. final MBBS University examinations.
157
mebooksfree.com
Chapter | 11 |
Hematology
– Due to splenomegaly (Hypersplenism)

11.1 Approach to a child with – Paroxysmal nocturnal hemoglobinuria
anemia j B) Intracorpuscular—
– Red cell membrane disorders (Hereditary
spherocytosis and elliptocytosis)
• Anemia is defined as reduced amount of – Red cell enzyme deficiencies (G6PD deficiency)
hemoglobin and reduction in oxygen carrying
– Thalassemia
capacity of RBCs
– Hemoglobinopathies
• High prevalence is seen in preschool children
(6–36 months of age)
• Hematopoietic disorders—
j Leukemia
• More common in rural areas as compared to urban j Aplastic anemia
population
j Myelodysplastic anemia
• WHO criteria for diagnosing Anemia (Hemoglobin
cut off below which a person is anemic)
• Blood loss (acute or chronic)
j Secondary to parasitic infections like hookworm,
j Children 6 months–5 years < 11 gm/dL
giardiasis, gastritis, peptic ulcer, polyps
j Children 6–14 years < 12 gm/dL
• Chronic illnesses
Etiology j Juvenile rheumatoid arthritis, renal disease, heart
• Inadequate dietary intake of iron and other nutrients diseases
like folic acid and vitamin B12 • Poisoning
• Inadequate supply at birth j Lead, arsenic and other heavy metals
j Prenatal or maternal nutrition deficiency Etiopathological classification of Anemia
j Prematurity
j Low birth weight Anemia due • Acute post-hemorrhagic anemia
• Inadequate absorption of iron to increase • Chronic blood loss due to some
j Gluten-induced enteropathy blood loss chronic disease e.g., hookworm
j Postgastrectomy infestation, ulcerative colitis, polyps
j Presence of phytates and calcium in the diet Anemia due • Deficient heme synthesis—iron
j Recurrent or chronic diarrhea to impaired deficiency anemia
• Excessive physiological demands of iron associated red cell • Vitamin B 12 or folic acid
with rapid growth periods production deficiency (megaloblastic anemia)
j Prematurity • Deficient globin synthesis—
j Preschool period thalassemia
j Adolescence • Aplastic anemia (acquired or
• Hemolytic anemias hereditary)
j A) Extracorpuscular— • Pure red cell aplasia
– Autoimmune hemolytic anemia • Anemia of chronic disorders
– Microangiopathic hemolytic anemia (chronic renal failure, cardiac
– Toxic effects due to infection disorders)
158
mebooksfree.com
Hematology Chapter | 11 |
Anemia due • Sickle cell anemia, thalassemia, • Peripheral smear examination

to increased hemoglobinopathies Presence of spherocytes—Hereditary
j
red cell • Autoimmune hemolytic anemia spherocytosis, immune hemolytic anemia

destruction • Hereditary spherocytosis j Presence of schistocytes—DIC, hemolytic uremic
(hemolytic • Paroxysmal nocturnal syndrome
anemia) hemoglobinuria j Presence of basophilic stippling—Hemolytic
anemia, lead or arsenic poisoning and
sideroblastic anemia
Clinical approach to anemia
• Coomb’s test to distinguish between immune and
No petechiae and With petechiae and hereditary hemolytic anemia
ecchymosis ecchymosis • Serum levels of iron, vitamin B12, and folic acid are
• Nutritional iron • Aplastic anemia determined in suspected cases of nutritional anemia
deficiency • Bleeding disorders
• Megaloblastic anemia • Idiopathic
• Pure red cell aplasia thrombocytopenic 11.2 Causes of microcytic
• Thalassemia purpura hypochromic anemia
• Red cell enzyme • Disseminated
deficiency intravascular
• Lead poisoning coagulation • Iron deficiency anemia
With With petechiae, • Thalassemia
hepatosplenomegaly lymphadenopathy, and • Hemoglobinopathies (HbS, HbD, HbE)
• Thalassemia hepatosplenomegaly • Anemia of chronic disease
• Hemoglobinopathies • Leukemia • Inflammatory disease
• Liver disorders • Myeloproliferative • Congenital dyserythropoietic anemia
• MDS disorders • Sideroblastic anemia (Lead poisoning)
• Infections • Pyridoxine deficiency
• Infiltrative disorders
Clinical features 11.3 Causes of macrocytic

• Early symptoms are lassitude and easy fatigability. hypochromic anemia
• Anorexia, irritability and poor school performance
• Severe anemia—Dyspnea on exertion, tachycardia,
palpitations Increased Reticulocyte Reduced or Normal
• Characteristic sign—pallor detected in nail beds, count Reticulocyte count
oral mucous membranes and conjunctiva
• Acute blood loss • Vitamin B12 and folate
• Mid systolic flow murmur is appreciated over • Chronic blood loss deficiency
pulmonary area in severe anemia • Autoimmune • Congenital
• Lymphadenopathy, Hepatosplenomegaly in hemolytic anemia dyserythropoietic anemia
malignancies and infections • Hemoglobinopathies • Myelodysplastic anemia
• Splenomegaly in kala azar, malaria, hemolytic anemia (HbS, HbD, HbE) • Liver disease
• Presence of petechiae or purpura indicates • Thalassemia • Hypothyroidism
concomitant thrombocytopenia
Investigations
• Complete hemogram 11.4 Causes of normocytic
Mean corpuscular Volume (MCV) denotes the
j
normochromic anemia
size of cell
j Mean corpuscular hemoglobin concentration
(MCHC) and Mean corpuscular hemoglobin
Increased Reduced or Normal
(MCH) provide information on red cell Reticulocyte count Reticulocyte count
hemoglobinization
• Red cell distribution width—Measure of variation • Acute blood loss • Anemia of chronic infections
in red blood cell size. Increased in Iron deficiency • Hemolytic • Chronic Renal Failure
anemia. anemia • Liver disease, Hypothyroidism
• G6PD deficiency • Aplastic anemia
• Reticulocyte count
j Distinguish between anemia caused by red cell • Pyruvate kinase • Leukemia, Myeloma,
deficiency Myelofibrosis and Infiltration
destruction and decreased production
159
mebooksfree.com
• Children present with non-specific symptoms like

11.5 Iron deficiency anemia irritability, anorexia, tiredness, weakness and cramps.
Examination often reveals pallor, atrophy of tongue
• Most widespread micronutrient deficiency. It is papillae, angular stomatitis, glossitis, koilonychias,
estimated to affect one-third of world population out and platynychia.
of which 90% cases are from developing countries. • Severe cases may have breathlessness, tachycardia and
Approximately 50% of cases are due to iron deficiency a soft systolic hemic flow murmur at the cardiac base.
• Other risk factors include limited iron stores at Severe cases can progress to ‘high output’ congestive
birth, immediate umbilical cord clamping at birth, cardiac failure.
delayed introduction of complementary foods and • Growth is invariably affected in severe cases causing
chronic infections ‘failure to thrive’.
• Infants, preschool children, adolescents and women • Rare presentations include diarrhea, pseudotumor
of childbearing age are at a greatest risk of developing cerebri and splenomegaly
iron deficiency • Craving and ingestion of inedible substances (Pica)
• Normal infants have about 75 mg/kg of iron, two is present in 70%–80% of cases. Common substances
thirds of which is present in RBCs include clay (geophagia), dirt, ice (pagophagia), chalk
• Infants and young children should continue to etc. Pica improves with iron therapy.
absorb 0.8–1.0 mg of iron daily to reach the adult • IDA also impairs cognitive abilities and can affect
level of stores of 4–5 g mental, social and emotional development. As iron
is a cofactor for many enzymes in cellular metabolic
Causes
pathways, IDA can depress immunity and predispose
• Decreased iron stores • Increased losses to secondary infections.
j Preterm j GI bleeding
Investigations
j Small for date babies j Malaria
j Twins j Hookworm
• Complete Hemogram
Hemoglobin is reduced
• Decreased intake/
j
infestation
assimilation j Peptic ulcer
j Total number of RBCs are reduced
j Delayed introduction j Bleeding diathesis
j MCV and MCHC reduced
of complementary feeds • Increased demands • Peripheral smear shows microcytic hypochromic red
j Malnutrition/Iron-poor j Prematurity,
cells with anisocytosis and poikilocytosis (Fig. 11.1)
diet/malabsorption LBW babies • Red cell distribution width (RDW—measure of RBC
syndromes j Recovering from cell size variability) is increased (>14.5%)
j Chronic infection/ protein energy • Serum levels of iron (<75 mg/dL) and ferritin
chronic diarrhea malnutrition (<15 ng/mL) are reduced
j Gastrointestinal surgery (PEM) • Total iron binding capacity is increased
j Adolescents (>470 µg/dL)
• Saturation of transferrin is reduced to less than 16%
Pathophysiology
• Body iron is regulated by absorptive cells in the
proximal small intestine
• Deficiency in older children is due to dietary
deficiency. Absorption is further impaired due to
dietary deficiency and decreased non heme iron
absorption
• Infants feeding on cow’s milk are more prone for iron
deficiency due to
j Iron in cow’s milk has lower bioavailability
j Bovine milk is rich in calcium that competes with
iron for absorption
j Gastrointestinal blood loss with cow’s milk allergy
Clinical features
• Careful history including type of milk, timing of
introduction of complementary foods in infants
should be noted. Peak incidence occurs between
6 months and 3 years followed by adolescents Figure 11.1 Microcytic hypochromic anemia seen in Iron
11–17 years. deficiency anemia.
160
mebooksfree.com
• Depletion of stainable iron from BM j Red cell transfusion are given in

• High free erythroprotoporphyrin precedes the anemia – emergency situation like severe anemia with
• Reticulocyte count is normal unless the child has congestive cardiac failure or
received iron therapy. – with ongoing blood loss
• In Severe cases, Chest X-ray, and Echo Heart should – when Hb levels are below 3–4 g/dL
be done to look for Cardiomegaly and signs of LVF j Packed red cells may be slowly given preferably
respectively 5–10 mL/kg at one time.
Treatment Prevention
• Cause of anemia should be identified and treated • Exclusive breastfeeding for 6 months
• Dietary counseling and treatment for the cause are • Timely introduction of complementary feeding at
required to prevent recurrence or failure of therapy 6 months
• Oral therapy • Iron supplementation for preterm/ LBW infants from
j Ferrous sulfate is most effective and started at 2 months
3–6 mg/kg/ day in 3 divided doses for 4–6 months • Restrict cow’s milk consumption
j Reticulocyte count increase in 72–96 h after • Intake of green leafy vegetables and sprouting green grams
initiating treatment • Periodic deworming in endemic areas
j Absorption is best if taken on an empty stomach • Iron supplements for susceptible infants and children
j Side-effects of oral iron therapy include nausea, and at puberty, especially in girls
vomiting, diarrhea, constipation, abdominal • National Nutritional Anemia Control Program
cramps, staining of teeth and tongue and recommends 20 mg of iron and 100 µg of folic acid
discoloration of stools. daily for 100 days every year
j Vitamin C enhances absorption of iron but foods
rich in phytates (cereals) and phosphates (milk)
reduces absorption. 11.6 Megaloblastic anemia
j Hemoglobin rise following oral iron therapy is
around 0.1 g/dL/day
• Megaloblastic anemia is characterized by macrocytic
Response to iron therapy in iron deficiency anemia: red blood cells and erythroid precursors that show
nuclear dysmaturity (ineffective erythropoiesis).
Time after Iron This type of anemia is caused by the deficiency of
administration Response either folic acid or Vitamin B12 or both and rarely
12–24 h Decreased irritability, increased due to inborn errors of metabolism.
appetite • Clinical features and hematological tests do not
26–48 h Erythroid hyperplasia differentiate between folic acid or B12 deficiency
48–72 h Reticulocytosis, peaking at 5–7 days Etiology
4–30 days Increase in Hb level (best measure)
• Decreased intake of
j Vitamin B12 (observed with strict vegetarian
1–3 months Replenishing iron stores diets, malnutrition)
j Folic acid (infants consuming goat milk)
• Parenteral therapy • Increased requirements
j Indications for parenteral therapy j Infancy
– Intolerance to oral iron j Pregnancy
– Malabsorption j Chronic hemolytic anemia
– Ongoing blood loss • Impaired absorption
j Commercially available preparations j Failure to secrete intrinsic factor
– Iron dextran j Celiac disease
– Iron sucrose j Malabsorption
– Iron ferric gluconate • Drugs
– Ferric carboxymaltose injection j Impaired cobalamin absorption—Proton pump
j Intravenous iron sucrose is safe and effective inhibitors
j Formula to calculate the dose of Iron j Impaired folic acid absorption—Phenytoin,
(mg) = Weight in kg × Hb deficit (g/dL) × 4 phenobarbitone
j Hb deficit is the difference between measured and j Interference with folate metabolism—
desired values of Hb. Methotrexate, trimethoprim, pyrimethamine
• Blood transfusions j Others —6-mercaptopurine, hydroxyurea,
j Rarely needed 5 flurouracil, zidovudine
161
mebooksfree.com
Pathophysiology
• Occurs due to impaired nuclear maturation. Methyl
tetrahydrofolate, a folic acid derivative needed
for synthesis of DNA nucleoproteins. Vitamin B12
needed as cofactor for folic acid recycling. Deficiency
of these two leads to delayed nuclear maturation
by impairing the nuclear progression. Despite
active erythropoiesis, there is premature cell death
(ineffective erythropoiesis)
Clinical features
• Early symptoms include Anemia, Anorexia,
Irritability, and easy fatigability
• Glossitis, stomatitis
• Hyperpigmentation of skin over knuckles and
terminal phalanges are specific findings seen in this
condition. Tremors, failure to thrive and delayed or
regression of milestones can be seen.
• In addition to the above symptoms, vitamin B12
deficiency can also cause neurological manifestations
j Neurological symptoms often precede the onset of
anemia Figure 11.2 Hypersegmented neutrophils.
j Loss of position and vibratory sensation
j Memory loss, confusion therapy of 100–250 µg/month given intramuscularly
j Posterior and lateral column deficits may appear to prevent recurrence. Oral vitamin B12 given is not
j Neuropsychiatric manifestations preferred due to poor patient compliance and erratic
• Neurological symptoms are uncommon in folic acid absorption
deficiency • Children with neurological complications should
Investigations receive vitamin B12 for 2 weeks followed by every
• Hemogram 2 weeks for 6 months and monthly for life long
j Anemia, leukopenia and thrombocytopenia • Anemia not responding to folate or B12 may
(Pancytopenia seen in 40%–70% cases) be secondary to rare metabolic disorders like
j Macrocytic red cells (>110 fl) homocystinuria or due to antimetabolic drugs
j Hypersegmented neutrophils (Fig. 11.2)
j Reticulocyte count—low
• Bone marrow is hypercellular because of erythroid 11.7 Approach to child with
hyperplasia
• Serum vitamin B12 and folic acid levels are reduced suspected hemolytic anemia
• Schilling test—used to differentiate between
pernicious anemia and malabsorption • Hemolytic anemias are group of conditions
• Elevated levels of lactate dehydrogenase and characterized by accelerated rate of red blood cell
indirect bilirubin destruction and impaired ability of bone marrow to
Differential diagnosis respond
• Aplastic anemia, Pure red cell aplasia, Fanconi’s • Divided into two types
anemia, Congenital dyserythopoietic anemia j Inherited
• Hypothyroidism, Myelodysplastic syndrome, HIV j Acquired
infection • Most intrinsic defects are inherited and the extrinsic
are acquired
Treatment
• Therapeutic dose of folate should be administered Causes
along with vitamin B12. However, folate therapy does Acquired
not correct neurological manifestations. Folate is given • Mechanical
for 3–4 weeks (1–5 mg/day) and continued for 1–2 j Macroangiopathic—artificial heart valves, march
additional months for the replenishment of body stores hemoglobinuria
• Vitamin B12 (500–1000 µg/dose) is given j Microangiopathic—DIC, hemolytic uremic
intramuscularly on alternate days for a period of syndrome, thrombotic thrombocytopenic purpura
2–3 weeks. This should be followed by maintenance • Infections—malaria, kala azar, Clostridium welchii
162
mebooksfree.com
• Antibody mediated—autoimmune hemolytic III. Features specific to etiology

anemia • Peripheral smear is useful in hemolytic anemia
• Transfusion reactions—immediate and delayed j Malarial parasites
• Hemolytic disease of new born j Bite cells—G6PD deficiency
• Hypersplenism j Spherocytes—hereditary spherocytosis
• Drugs—cefotetan, ceftriaxone j Microcytes with fragmented RBC—thalassemia
• Physical injury—Burns j Thrombocytopenia with schistocytes—
• Chemical injury—snake bite, lead, and arsenic DIC/HUS
toxicity • Coomb’s test helps to determine the etiology of
hemolysis
Inherited
• Hemoglobinemia, hemoglobinuria,
• Hemoglobinopathies—thalassemia, sickle cell hemosiderinuria are present in intravascular
disease hemolysis
• Red cell membrane defects—Hereditary • Similar to intravascular hemolysis unconjugated
spherocytosis bilirubin, lactate dehydrogenase and reticulocyte
• Red cell enzymopathies—G6PD deficiency count are elevated in extravascular hemolysis
• Unstable hemoglobins
Management
• Lipid membrane defects—abetalipoproteinemia
• Porphyria
• Maintain fluid balance and renal output during and
after hemolysis
Clinical features • Blood transfusions are useful in acute anemia
• Anemia—weakness, pallor and fatigue • Transfused RBCs can also undergo hemolysis if
• Jaundice pathology persists.
• Red urine suggests hemoglobinuria in intravascular • AIHA is treated with corticosteroids (prednisolone
hemolysis 1–2 mg/kg/day) and tapered over months after
• Splenomegaly hemolysis has resolved
• Gallstones
• Hemolytic facies
• Leg ulcers (sickle cell anemia)
11.8 Hereditary spherocytosis (HS)
Investigations
• Reticulocyte count is useful in determining the rate
of red cell destruction • HS results from a deficiency or defect in RBC
• Laboratory findings are divided into three groups cytoskeleton spectrin or its anchoring proteins
j Increase in erythrocyte destruction and ankyrin. These proteins play a vital role in
j Compensatory increase in rate of erythropoiesis maintaining the shape and stability of red cell
j Features specific to particular etiologies of membrane. This abnormality predisposes to
hemolytic anemia early destruction and decreased life span of red
blood cells.
I. Laboratory signs of accelerated erythrocyte • Hemolysis, intermittent jaundice, splenomegaly and
destruction spherocytes in the peripheral smear are morphologic
• Fall in hemoglobin level at >1.0 g/dL per week hallmarks of this condition
• Increased serum level of unconjugated bilirubin • This disorder is transmitted predominantly as an
• Increased urinary urobilinogen excretion autosomal dominant trait, less commonly, as an
• Increased serum lactate dehydrogenase autosomal recessive disorder
• Reduced haptoglobin and hemopexin Clinical features
• Reduced glycosylated hemoglobin
• Presents during infancy or childhood with anemia.
• Decreased erythrocyte life span Fatigue and exercise intolerance are predominant
II. Laboratory signs of accelerated erythropoiesis symptoms of anemia in children. Anemia is
Peripheral blood typically mild (Hb 9–11 g/dL). However, inter-
• Polychromasia or reticulocytosis current infection may precipitate significant
• Macrocytosis hemolysis.
• Increase in nucleated red cells • Icterus usually presents during early childhood but
Bone marrow can also be intermittent. Some cases can present with
• Erythroid hyperplasia severe neonatal jaundice requiring phototherapy or
• Iron kinetic studies exchange transfusion.
• Increased plasma iron turnover • Mild to moderate splenomegaly in the first year of
• Increased erythrocyte iron turn over life, based on the rate of hemolysis
163
mebooksfree.com
• Frontal bossing
• Gallstones—Pigment calculi due to increased 11.9 Glucose-6-phosphate
bilirubin excretion dehydrogenase deficiency
• Parvovirus B19 infection can rarely precipitate (G6PD Deficiency)
Aplastic crisis in susceptible children.
Investigations
• G6PD deficiency is the most common red
• Hemoglobin—6–10 g/dl cell enzyme deficiency. It is highly prevalent in
• MCV—decreased, MCHC—increased—Microcytic central Africa, Mediterranean, Middle East and
hypochromic anemia in India.
• RDW—increased due to spherocytes • G6PD deficiency is X linked recessive disorder.
• Peripheral smear shows polychromatophilic Though only males are affected, rarely female can be
reticulocytes and the characteristic ‘spherocytes’. affected due to incomplete lyonization
Spherocytes are smaller than the normal red cell
• G6PD is required in Embden–Meyerhof pathway
and is devoid of central pallor to generate nicotinamide adenine dinucleotide
• Markers of Hemolysis—Raised LDH, Reduced (NADH) and ATP and in hexose monophosphate shunt
Haptoglobin to generate nicotinamide adenine dinucleotide
• Reticulocyte count—high in hemolytic crisis phosphate (NADPH). NADPH has the role of
• Indirect hyperbilirubinemia reduction of glutathione which protects hemoglobin
• Eosin-5-maleimide (EMA) fluorescent dye test: from oxidative damage
Reduced binding with dye indicates HS.
• There are four main syndromes associated with G6PD
• Common diagnostic screening test used is osmotic deficiency
fragility test j Neonatal jaundice
j Favism
Diagnosing Hereditary spherocytosis j Chronic nonspherocytic hemolytic anemia
• Positive family history j Drug-induced hemolytic anemia
• Typical clinical and laboratory features
• Splenomegaly Drugs precipitating G6PD
• Spherocytes and reticulocytes in smear
• Elevated MCHC Antibacterials Antimalari- Antihel- Others
Sulfonamides als minths Vitamin K
Dapsone Primaquine β-Naphthol analogs
Differential diagnosis Trimethoprim- Pamaquine Stibophen Methylene
• Spherocytes are also seen in sulfamethox- Chloro- Niridazole blue
j ABO incompatibility azole quine Toluidine
j Immune-mediated hemolytic anemia Nalidixic acid Quinacrine blue
j Burns Chlorampheni- Probenecid
j Clostridium perfringens sepsis col Dimercap-
Nitrofurantoin rol
Treatment
Acetylsali-
• Blood transfusion may be required on a regular basis cylic acid
in severe cases.
• Splenectomy is treatment of choice for patient
with severe hemolysis and high transfusion Pathogenesis
requirement and should be performed • Following oxidant exposure, hemoglobin is converted
beyond 6 years. Post splenectomy penicillin to methemoglobin and denatured to inclusion bodies
prophylaxis is given till adulthood along with (Heinz bodies). These heinz bodies get attached to
vaccination against capsulated organisms to red cell membrane and aggregate intrinsic membrane
prevent sepsis proteins. Reticuloendothelial cells detect these
• Immunization against Hemophilus influenza type B, changes as antigenic sites which leads to preferential
Streptococcus pneumoniae and Nisseria meningitidis phagocytosis of the cells
are given for splenectomy patients • Partly phagocytosed cell (bite cell) has a shortened
• Lifelong folate supplementation and prevention of half life
iron deficiency Clinical features
• Cases are prone for developing parvovirus infection • Asymptomatic unless triggered by infection, drugs or
leading to aplastic crisis and patients usually recover ingestion of fava beans
in 4–6 weeks • Presents in neonatal period with severe jaundice
• Cholecystectomy in case of symptomatic gallstone requiring exchange transfusion
164
mebooksfree.com
• Hemolysis occurs 24–48 h post exposure to triggers • Primary autoimmune hemolytic anemia
• Hemolytic crisis manifests with pallor, icterus, j Occurs without any baseline immune disorder or
hemoglobinemia, hemoglobinuria, and precipitating factors
splenomegaly j Seen at any age with male predominance
• Favism • Secondary autoimmune hemolytic anemia
j Acute intravascular hemolysis may be precipitated j Occurs as a part of systemic illness or due to
by exposure to the broad bean vicia faba immune disorder
j Pallor, jaundice, and hemoglobinuria are the j More common in adolescents, young adults and
clinical hallmarks in females
Investigations
Primary autoimmune Secondary
• Diagnosis is suggested by family history, clinical hemolytic anemia autoimmune hemolytic
findings, laboratory findings, and exposure to • Warm-reactive antibody anemia
oxidants prior to hemolytic event (mainly IgG) • Underlying
• Following hemolysis there is fall in hemoglobin and • Cold agglutinin disease autoimmune
hematocrit (mainly IgM and disorders, e.g.,
• Plasma haptoglobin and hemopexin are low and complements) systemic lupus
serum LDH levels are elevated • Paroxysmal cold erythematosus,
• Peripheral smear shows fragmented bite cells and hemoglobinuria Evan’s syndrome
polychromasia (mainly IgG and • Drug induced, e.g.,
• Special stains demonstrate heinz bodies following complements) penicillin
few days of hemolysis • Immunodeficiency,
• In between hemolysis, all patients show normal e.g., HIV, Primary
blood picture. immunodeficiency
• Glucose-6-phosphate dehydrogenase enzyme assay • Specific infections,
confirms the diagnosis e.g., mycoplasma
• DNA analysis is useful for heterogeneous females infection
• Malignancies,
Treatment e.g., lymphomas,
• Supportive care during acute crisis (Hydration, leukemia
monitoring and transfusion if needed). Severe
hemoglobinuria can lead to acute tubular necrosis
and renal failure. Intravenous sodium bicarbonate is Clinical forms of AIHA
given to alkalize urine and prevent hematin clots in Warm reactive autoantibody
the renal tubules. • Caused by autoantibody of IgG class that binds the
• Folic acid supplementation and avoidance of red cell antigens at 37°C, causing extravascular
triggering factors hemolysis by fixing the complements
• Phototherapy, exchange transfusion in neonatal • Warm-reactive IgG antibody-sensitized red cells are
period preferentially removed in spleen. If IgG antibody also
fixes and activated complements, it will be recognized
by the macrophages with receptor to C3b, mainly in
the liver
11.10 Autoimmune hemolytic
Cold reactive autoantibody
anemia (AIHA) • Caused by autoantibody of IgM class that binds
red cell antigen at below 37°C efficiently fixes
• Autoimmune response targeting red cells may complements and leads to intravascular hemolysis
occur in isolation or as a complication of infection. and rarely IgG antibody [in paroxysmal cold
Abnormal antibodies directed against red blood cells hemoglobinuria (PCH)]
are produced endogenously • Often have chronic illness with intermittent relapses
• Characterized by shortened red cell life, hemolysis, and remissions, need long-term therapy and develop
and anemia treatment-associated complications
Classification • Cold agglutinin disease is characterized by a massive
• Autoimmune hemolytic anemia can be classified increase in the cold antibodies following a viral
in various ways depending on the type of infection or mycoplasma pneumonia. This leads
autoantibody, site of hemolysis or the precipitating to intravascular hemolysis and hemoglobinuria on
illness exposure to cold.
165
mebooksfree.com
• Paroxysmal cold hemoglobinuria is classically • HbA2 is constituted by two pairs of α chains and
associated with syphilis. It occurs due to a specific two pairs of δ chains (α2δ2)
antibody known as “Donath–Landsteiner hemolysin”, • Deficiency or abnormalities in any of the Hb chains
it has anti-P specificity. leads to thalassemia syndromes or abnormal
Clinical features hemoglobinopathies
• History suggestive of nonspecific viral infection in Classification
recent past • The α gene is present on chromosome 16 and β gene
• Acute onset Anemia will present with fatigue, represented on chromosome 11
lassitude, and giddiness • Inherited as an autosomal recessive disease and
• Dark urine, Acholuric jaundice, and splenomegaly there is 25% chance that children born in each
Investigations pregnancy will develop thalassemia major
• Complete hemogram • Thalassemia is classified depending on the deficiency
j Normocytic normochromic anemia of type of globin chain of Hb
j Reticulocyte count is increased
Classification of thalassemia syndromes
• Peripheral smear shows polychromasia, anisocytosis,
spherocytes, and nucleated RBCs α-thalassemia ß-thalassemia
• Coombs test—to detect presence of autoantibody
and or complement C3 on red cell A. Silent carrier A. Silent carrier
j No anemia, normal j Asymptomatic,
• Direct antiglobulin test is positive in most of the cases
red cells Anemia absent
Management j 1–2% Hb Bart’s (4g) j Hemoglobin
• Medical management of underlying disorder at birth pattern is
• Warm autoimmune hemolytic anemia B. α-Thalassemia trait normal,
j Prednisolone 1 mg/kg for 4 weeks till j Mild anemia, diagnosed by
hemoglobin is stable then tapered over hypochromic globin chain syn-
4–6 months microcytic red cells thesis analysis
j IV immunoglobulin 1 mg/kg/day for 2 days j 5%–10% Hb Bart’s B. Thalassemia trait
j Splenectomy can offer remission in 50% cases (4 g) at birth j Mild anemia,
j In severe cases or cases unresponsive to C. Hemoglobin H (Hb H) hypochromic mi-

conventional therapy, immunosuppressive disease crocytic red cells
agents like cyclophosphamide, azathioprine and j Moderate j Does not require
cyclosporine can be tried hypochromic, transfusion

j Rituximab (monoclonal antibody to B cell CD20) microcytic anemia j Elevated
j 5%–30% HbH HbA2 > 3.4%

given for refractory cases
D. Hydrops fetalis C. Thalassemia
• Cold autoimmune hemolytic anemia
j Self-limiting and supportive care is needed j Death in utero intermedia
caused by severe j Moderate
j Acute episode is treated with prednisolone and
anemia anemia; not
IVIG
j Predominantly Hb dependent
Plasma exchange is effective in severe cases
Bart’s, small amount on blood
j
Prognosis of HbH transfusion for

• Warm AIHA are at greater risk for severe and chronic their survival.
disease with higher mortality and morbidity j May require
• Cold AIHA or paroxysmal cold hemoglobinuria has a occasional

self-limiting course transfusion
j Elevated HbF
D. Thalassemia major
j Depend-
11.11 Thalassemia ent on blood
transfusion for
• The hemoglobin consists of two pairs of amino acid their survival.
j Requires
chains: a pair of α chains and non- α chains
multiple
• Adult hemoglobin (HbA) consists of two pairs of
α chains and two pairs of β chains (α2β2) transfusions
j Markedly
• Fetal Hb is constituted by of two pairs of α chains elevated HbF
and two pairs of γ chains (α2γ2)
166
mebooksfree.com
Pathophysiology
Presentation
• Severe pallor • High performance liquid chromatography
• Symptoms of anemia—irritability, intolerance to j Hemoglobin electrophoresis - Hb F, A & A2
exercise, heart murmur estimation (Gold standard test)
• Hepatosplenomegaly • Iron studies shows
• Icterus—mild to moderate due to iron overload and j Increased Serum iron
liver dysfunction j Total iron binding capacity is normal
• Hemolytic (Chipmunk) facies j Serum ferritin is increased
j Frontal bossing, Depressed nasal bridge • Osmotic fragility test—reduced fragility
j Prominent facial bones, caput quadratum • Xray skull shows hair on end appearance due to
j Dental malocclusion and protrusion of teeth widening of diploic space
• Hyperuricemia Treatment
• Bony abnormalities due to extramedullary Management of thalassemia major should include
hematopoiesis • Correction of anemia—packed red cell
Investigations transfusions
• Complete blood count • Management of complications of blood transfusions
j Hemoglobin ranges from 2–8 gm/dL • Management of transfusion transmitted diseases—
j MCV and MCH are low Hepatitis B, hepatitis C, HIV, malaria, CMV, Yersinia
j Reticulocyte count is elevated • Removal of excess iron—Chelation therapy
j Leukocytosis with shift to left • Management of endocrine and cardiac complications
j Platelet count is normal j Curative treatment—BMT/SCT
• Peripheral smear shows j Hypersplenism—role of splenectomy
j Marked hypochromasia and microcytes • Management of other complications
j Nucleated RBC j Gall stones/anemia/hypoxia/leg ulcers
j Basophilic stippling j Pharmacological methods to increase gamma
j Immature leukocytes chain synthesis
167
mebooksfree.com
• Future treatment—Gene replacement therapy, Painful Abdominal Crisis

intrauterine BMT • Painful abdominal crisis occurs due to localized areas
• Prevention of disease by antenatal diagnosis and of bowel dysfunction
genetic counseling • Severe abdominal pain and signs of peritoneal
• Hydroxyurea—15–20 mg/kg /day used to increase irritation
HbF and reduce need for blood transfusion in other • Usually resolves in a period of 3–5 days
thalassemic states • Management consists of bowel rest, maintenance of
Complications hydration by intravenous fluids
• Iron overload—treated with chelation therapy with Acute Chest Syndrome
desferrioxamine • Occurs due to vaso-occlusion of pulmonary vessels
• Hypersplenism • Presents with chest pain, cough, tachypnea,
• Osteoporosis and osteopenia hypoxemia, fever
• Extramedullary hematopoiesis • Leads to infarction and pulmonary sequestration
• Blood transfusion related reactions and infections • Treatment includes oxygen support, hydration,
• Psychological complications antibiotics, bronchodilators
Cerebrovascular accidents
• Stroke occurs in 6%–17% patients
11.12 Sickle cell anemia • Common age group is 3–10 years
Sequestration crisis
• Autosomal recessive inheritance • Sudden trapping of large amount of blood in spleen
• Disease results from the substitution of valine for or less commonly in liver
glutamic acid at position 6 of the beta globlin gene • Splenic dysfunction occurs due to obstruction of
• Homozygous state for HbS gene manifest as sickle sinusoidal blood flow
cell disease Aplastic crisis
• Heterozygous state for HbS gene have sickle cell trait • The causative organism is Parvovirus B19
Pathophysiology • The child presents with acute anemia, without
• The soluble form of Hb changes to gel form when Hb reticulocytosis
“S” is deoxygenated and deforming the RBC to sickle • Condition is always self-limiting with duration of
shape which has more fragile membrane 7–10 days
• Upon reoxygenation sickle cell regains its original Other clinical features
shape • Priapism, Megaloblastic crisis, Epistaxis, Retinal
• Repeated sickling and unsickling leading to infarcts
irreversible sickle cell formation • Renal involvement—Hyposthenuria, nephrotic
• These red cells are rapidly hemolyzed and have a life syndrome
span of 10–20 days • Gall stones, Delayed somatic and sexual growth
• Sickle cells damage the endothelial cells leading to
Investigations
subendothelial infiltration and narrowing of the vessels
• Platelets aggregate over the adherent red cells • Anemia and thrombocytopenia
and damaged endothelium, causing blockage of • Leukocytosis; Shift to left indicates infection
microvasculature and tissue ischemia • Peripheral smear shows sickle shaped cells
(Fig. 11.3)
Clinical features • Presence of Howell jolly bodies indicates
Vaso-occlusive crisis asplenism
• Occurs due to obstruction to microvascular • Sickling test (using sodium metabisulfite)
circulation by sickled red cells • Hemoglobin electrophoresis
Hand foot syndrome • Radiograph of chest and bones are taken during crisis
• Swelling over the affected bones with severe pain period
and tenderness Management
• Most marked in small bones of hands and feet • Hydration and analgesics are mainstay of treatment
• Dactylitis • Oxygen supplementation if hypoxia is present
Avascular Necrosis • Blood transfusion is useful in patients with aplastic
• Avascular necrosis of bone occur secondary to crisis and acute sequestration crisis
vasoocclusion of nutrient artery • Exchange blood transfusion is indicated in case
• Femoral head, humerus, upper-third of tibia can be of cerebrovascular accidents and acute chest
affected syndrome
168
mebooksfree.com
j Radiation
j Viruses—Hepatitis, Epstein–Barr virus, Parvovirus
j Pregnancy
j Paroxysmal nocturnal hemoglobinuria
j Miscellaneous: Hypogammaglobulinemia,
Thymoma, Eosinophilic fasciitis
Inherited
• Fanconi’s anemia
• Dyskeratosis congenita
• Reticular dysgenesis
• Shwachman–Diamond syndrome
Clinical features
• Thrombocytopenia will lead to bleeding
manifestations like skin bleeds, mucosal bleeds, GI
tract, hematuria, menorrhagia, and rarely intracranial
hemorrhage
• Neutropenia will lead to infection and fever with or
without localization of infection
• Anemia appears last and if severe will lead to
fatigue, breathlessness, puffiness, edema of feet and
Figure 11.3 Peripheral smear showing ‘sickle cell’. congestive cardiac failure (CCF)
Investigations
Prevention • Peripheral blood
• All children should receive prophylaxis with j Anemia with normal RDW, normocytic
penicillin or amoxycillin at least until 5 years of age normochromic RBCs, occasional macrocytosis
• Immunization against pneumococcal, with corrected retic count < 1%
meningococcal, hemophilus influenza type B j Leukopenia with decreased ANC
infection j Thrombocytopenia: Decreased platelet count with
• Lifelong folate supplementation normal MPV
• Hydroxyurea—increases HbF and reduces painful • Stress erythropoiesis: Raised fetal hemoglobin (HbF)
crisis episodes and i antigen in some patients
• Genetic counselling and testing should be offered to • Coagulation parameters are usually normal
the family • Iron study may show iron overload
• Antenatal diagnosis can be done at 8–10 weeks of • Bone Marrow biopsy show hypocellular marrow
gestation, with chorionic villus biopsy, or amniocentesis with empty spicules, increased fat spaces,
hypoplasia, may be patchy, especially early in the
disease
• Stress cytogenetics done to rule out Fanconi’s
11.13 Aplastic anemia anemia
Treatment
• Disorder of hematopoietic stem cells resulting in • Supportive care includes the following
suppression of one or more of erythroid, myeloid j Packed red cells transfusion for severe anemia
and megakaryoctic cell lines j Platelet transfusion for severe thrombocytopenia
• Affects all age groups, but a small peak occurs at the j Antibiotics for infections
age of 5–6 years • Hematopoietic stem cell transplant (HSCT) is
• It may be inherited or acquired definitive therapy
Causes • Indication for HSCT are
Acquired j Young age
• Idiopathic j Severe aplastic anemia
• Secondary j Availability of matched sibling
j Drugs—sulfa, anticancer drugs, antiepileptics, • Patient not fit for HSCT can benefit from
chloramphenicol, gold, carbamazepine, antithymocyte globulin or antilymphocyte globulin
indomethacin, phenylbutazone along with cyclosporine
j Chemicals, e.g., benzene, sniffing glue, insecticides, • Immunosuppressive therapy is contraindicated in
dyes fanconi’s anemia and HSCT is the only cure
169
mebooksfree.com
• Until engraftment occurs patient needs multiple red

11.14 Hematopoietic stem cell cell and platelet transfusion during 2–3 week period
transplant (HSCT) of pancytopenia
• Life saving for severe malignant and non-malignant

disorders 11.15 Approach to a bleeding child
• Types of HSCT
j Autologous—stem cells harvested from the patient • Bleeding may occur due to defects in platelets,
j Allogenic—stem cells are collected from a coagulation disorders or dysfunctional
donor, either HLA matched sibling or unrelated fibrinolysis
person A) Qualitative disorders of platelet function
Indications for HSCT Inherited Acquired
Nonmalignant • Glanzmann’s • Medications
Malignant disorders disorders thrombasthenia • Chronic renal failure
(GP Ib deficiency) • Cardiopulmonary
• Acute myeloid leukemia • Thalassemia • Bernard soulier bypass
• Chronic myeloid leukemia • Aplastic anemia syndrome (GP IIb—III
• Acute lymphoblastic • Fanconi anemia a deficiency)
leukemia • Immunodeficiency • Gray platelet syndrome/
• Hodgkin disease syndromes Dense body deficiency
• Non hodgkin lymphoma • Inborn errors of
• Neuroblastoma metabolism
• Ewings sarcoma B) Coagulation disorders
• Myelodysplastic syndrome
Inherited Acquired
• Gliomas
• Hemophilia A and B • Liver disease
• Von Willebrand disease • Vitamin K
Allogenic HSCT • Specific factor deficiency deficiency
Donor requirement • Factor VII, X, XIII • Warfarin overdose
• Ideal donor is HLA identical sibling deficiency • Disseminated
• ABO blood group compatibility is not essential for • Afibrinogenemia intravascular
HSCT coagulation
• Successful transfusion causes the change of blood
group of recipient with that of donor
Pathogenesis
Myeloblastic conditioning • Hemostasis is a process involving platelets, vessel wall
• High doses of chemotherapy are given to suppress the and plasma proteins in a fine balance between blood
bone marrow in order to flow and local response to vascular injury
j Eradicate malignant cells • Plasma proteins involved in hemostasis perform three
j Suppress host immune to avoid allograft rejection functions
j Clear a physical space for adequate growth of j A multiple step zymogen pathway leading to
donor stem cell thrombin generation
Non myeloblastic conditioning j Thrombin induced formation of fibrin clot
• Donor T cells are used to eradicate both j Complex fibrinolytic mechanism limit clot
nonmalignant and malignant cells of host origin propagation
Technical aspects • Insoluble fibrin formed by these process and
activation of platelets form a hemostatic plug
• Bone marrow is harvested by repeated aspiration from
posterior iliac crest • The coagulation cascade involves two major pathways
Intrinsic pathway—measured by prothrombin
• Minimum number of marrow cells required are j
1–3 × 108 /kg time

Extrinsic pathway—measured by activated partial
• After transfused donor marrow cells reach host j
marrow space and start engrafting thromboplastin time

• Engrafting is successful when absolute neutrophil Clinical evaluation
count exceeds 500/mm3 on 3 successive days • History including onset of bleeding, type of bleeding
• During period for engrafting for 2–3 weeks intensive and precipitating factors should be noted as it helps
support and protective isolation are needed in defining the cause
170
mebooksfree.com
• In case of recent onset of bleeding Investigations

j With rash—henoch schonlein purpura • Hemogram is done for
j Icterus—liver failure j Platelet count
j Prodromal diarrhea or renal failure—hemolytic j Morphology of platelet and red cells
uremic syndrome j Evidence of microangiopathic hemolysis
• History of blood transfusion and family history • Activated partial thromboplastin time, prothrombin
of bleeding time and bleeding time
• Disorder affecting only boys suggest
X linked disorder like hemophilia while
in girls, autosomal dominant conditions 11.16 Idiopathic thrombocytopenic
like von Willebrand disease should be purpura (ITP)
suspected
• Poor wound healing and prolonged
bleeding from umbilical stump—factor VIII • Immune thrombocytopenia due to autoantibody
deficiency mediated consumption of platelets
• Presence of splenomegaly suggests infection, • Presents between 1 and 7 years of age
malignancy, collagen vascular disorders or • Two types based on duration of thrombocytopenia
hypersplenism j Acute—lasting less than 6 months
• History of medication intake like anticonvulsants, j Chronic—more than 6 months
penicillin, warfarin, aspirin, NSAIDs are noted Pathogenesis
• Platelet disorders • Secondary to antibodies directed against the
j Bleeding in skin and mucus membranes platelet glycoprotein IIb/IIIa complex
j Lesions range from pinpoint petechiae to small • Platelets with antibody on surface are trapped in
and superficial ecchymoses spleen
j Bleeds following minor trauma and surgery • These are removed by splenic macrophages
• Coagulation disorders • Mechanism of production of antibodies is not
j Bleeding into soft tissues, joints, muscle leading to known
large and deep ecchymoses • Increased megakaryocyte number in the bone
j Hemarthrosis is common with delayed bleeding marrow is hallmark of immune mediated platelet
after surgery destruction
Diagnostic Algorithm
171
mebooksfree.com
Clinical features Incidence of different sites of bleeding:

• Antecedent history of febrile illness but usually • Hemarthrosis: 70%–80%
afebrile at presentation • Muscle/soft tissue: 10%–20%
• Signs and symptoms depends on platelet count • Other major bleed: 5%–10%
• Presents with sudden appearance of bruises and • CNS bleed: < 5%
mucosal bleeding
Treatment
• Epistaxis, oral oozing, prolonged bleeding with
superficial trauma • Appropriate factor replacement
• Petechiae and ecchymoses • Judicious physiotherapy to prevent chronic joint
disease
• Healthy child without any hepatosplenomegaly,
lymphadenopathy and bony tenderness • Counselling for injury prevention
• Monitoring development of factor VIII and IX
Investigations inhibitors
• Complete blood count show low platelet count and • Desmopressin, synthetic analogue of vasopressin
other hematological parameters are normal can induce factor VIII levels and is tried in mild
• Circulating platelets are larger in size cases
• Bone marrow examination shows increased • Acute bleeds should be treated early (within 2 h if
megakaryocytes possible)
Management • Cryoprecipitate and fresh frozen plasma are used to
• Routine Platelet transfusion should be avoided control bleeding
• Children with active bleeding should be given • Cryoprecipitate doesn’t contain factor IX so it cannot
intravenous immunoglobulin 1 g/kg/day for be used in hemophilia B
1–2 days or 50–75mg/kg of anti D-immunoglobulin • IM injection and arterial puncture must be
in Rh positive children avoided
• Prednisolone 1–4 mg/kg/day for 2–4 weeks then
tapered Hemophilia A Hemophilia B
• Dexamethasone at 20 mg/m2 over 4 days every
3 weeks for 4–6 courses Hemarthrosis 40 IU/kg FVIII 60–80 IU/kg
• Refractory cases—immunosuppressive drugs conc. on D1, then FIX conc. on
like vincristine, cyclosporine, azathioprine, rituximab 20 IU/kg on D2, 3, D1, then 40
5 until joint func- IU/kg on D2, 4
• Serious hemorrhage—platelet transfusion under cover
tions normal or
of steroids
back to baseline
Muscle or 20 IU/kg FVIII 40 IU/kg FIX
subcutaneous conc., may need conc,may need
11.17 Hemophilia hematoma every other day treatment
treatment until every 2–3 days
resolved until resolved
• Most common hereditary clotting defects
• Hemophilia A is caused by factor VIII deficiency Mouth and 20 IU/kg FVIII 40 IU/kg
• Hemophilia B is caused by factor IX deficiency tooth conc., antifibrino- FIX conc.,
• Manifestations of hemophilia depends on level of extraction lytic therapy antifibrinolytic
clotting factors in blood therapy
Clinical features
Clotting factor
Severity (% activity) Bleeding episodes 11.18 Disseminated intravascular
Mild 5–40 Severe bleeding with
coagulation (DIC)
major trauma or surgery
Moderate 1–5 Mild spontaneous • Massive activation of coagulation that occurs inside
bleeding, severe bleed- the blood vessels, leading to deposition of fibrin in
ing with trauma, surgery the small vessels, thus decreasing blood supply to
Severe Spontaneous bleed- major organ systems
<1
ing predominantly in • Can range from isolated derangement of
joints and muscles laboratory parameters to severe bleeding from
multiple sites
172
mebooksfree.com
Etiology
Conditions associated with disseminated

intravascular coagulation
Infections Tissue injury/organ
• Bacterial sepsis (Meningococcus, failure
Staphylococcal, Streptococcal, • Massive head in-
Escherichia coli, Salmonella) jury, crush injury
• Viruses (HIV, • Hypoxia/hypop-
cytomegalovirus, herpes, erfusion, Shock
rubella, Acute-hepatitis, Reye • Cardiac arrest,
syndrome) Hypothermia
• Fungal (Histoplasma, • Heat stroke
Aspergillosis) • Fat embolism
• Protozoal (Malaria, Kala-azar) • Massive burns
• Rickettsial(Rocky mountain • Pancreatitis
spotted fever)
Immunological conditions Neonatal
• Systemic lupus • Dead twin
Figure 11.4 Pathophysiology of DIC.
erythematosus • Abruptio
• Autoimmune hemolytic placentae
anemia • Necrotizing Pathophysiology (Fig. 11.4)
• Crohn’s disease/ulcerative enterocolitis
colitis • Congenital • Three main pathological process involved
• Transfusion reactions(ABO infections j Initiation of fibrin deposition
incompatibility) • Respiratory j Amplification role of thrombin
• Transplant rejections, distress j Propagation of fibrin deposition
Graft versus host syndrome Clinical features
disease • Bleeding at venipucture site or surgical incision
Vascular abnormalities Gastrointestinal • Petechiae and ecchymoses
• Kasabach–Merritt syndrome • Fulminant hepa- • Shock
• Large vascular aneurysms titis Laboratory findings
• Coarctation of aorta • Severe inflam- • Identifying the underlying etiology
• Large prosthetic arterial grafts matory bowel
• Hemogram shows thrombocytopenia and smear
disease
shows schistocytes
• Prothombin time, activated partial thromboplastin
Malignancy Miscellaneous time and thrombin time are prolonged
• Acute promyelocytic • Snake bites • Fibrin degradation products or D–dimer increased
leukemia • Insect bites • Serum fibrinogen remain normal for long time
• Acute monoblastic leukemia • Recreational
• Lymphoproliferative disorders drugs Treatment
• Hemophagocytic • Poisoning: • Managing underlying disease
lymphohistiocytosis acute iron • Replacement Therapy in patients who are bleeding
• Solid tumors toxicity or those who are at risk of bleeding. This is done to
(neuroblastoma) • Massive restore consumed platelets and coagulation factors
transfusions • Anticoagulation with heparin to inhibit the
• Infusion of activation of intravascular coagulation in DIC
activated • Antifibrinolytic agents have limited benefit in
prothrombin patients with bleeding
complex
concentrates Scoring system for disseminated intravascular
Thrombotic disorders coagulation
• Homozygous protein C Risk assessment
deficiency Do the patients have an underlying disorder known to
• Antithrombin III be associated with overt DIC?
deficiency • If yes: Proceed
• Heparin-induced thrombosis • If no: Do not use this algorithm
173
mebooksfree.com
Platelet count Score Elevated FDP Score • Signs of arterial thrombosis

Diminished or absent peripheral pulses
>100,000/mm3 0 No increase 0
j
j Cool extremities
50,000–100,000/ 1 Moderate 2 • Manifestations of pulmonary embolism
mm3 increase j Anxiety, Breathlessness, Pleuritic chest pain
<50,000/mm3 2 Strong increase 3 j Fever, Tachypnea
Prothrombin Score Fibrinogen Score • Central nervous system thrombosis
time level j Vomiting, Lethargy
<3s 0 > 1 g/L 0 j Seizures, Weakness in an extremity
1 1
• Renal vein thrombosis
> 3 but < 6 s < 1 g/L
j Flank pain and Hematuria
>6s 2
Investigations
Cumulative score • Complete blood count
• 5: compatible with overt DIC. Repeat score daily • Peripheral smear
• < 5: suggestive for nonovert DIC. Repeat every • Prothombin time
1–2 days • Activated partial thromboplastin time
• Fibrinogen level
• DIC should be ruled out by doing D-dimer
levels
• Color doppler shows absence of signals in
11.19 Approach to child with thrombosed vessel
thrombosis • Echocardiography is useful for vena caval and
subclavian artery thrombosis
• Incidence of thrombotic diseases are less common in • Magnetic resonance venography used to detect
children central venous thrombosis
• Thrombosis is associated with significant morbidity • Chest radiography, D-dimer assay and VQ scan done
and mortality in children to rule out pulmonary embolism
• Levels of thrombin inhibitors (antithrombin,heparin Management
cofactor II, protein C and S) are reduced at birth and • Screening test for hypercoagulable state should be
during infancy done before initiating treatment
• Incidence of thrombosis is maximal at infancy and • Unfractionated or low molecular weight heparin is
adolescence used followed by warfarin
Factors increase the risk of thrombosis • Close monitoring should be done to prevent
• Acquired conditions overdosage and risk of bleeding
j Infections—bacterial, viral sepsis • The international normalized ratio (INR)
j Disseminated intravascular coagulation should be in the range of 2–3
j Dehydration • Duration of therapy depends on risk of
j Surgery/ trauma recurrence
j Cyanotic congenital heart disease Prognosis
j Antiphospholipid antibody syndrome • Recurrent thrombosis may occur due to inadequate
j Acute lymphoblastic leukemia anticoagulation therapy
j Nephrotic syndrome • Risk of recurrence
• Inherited conditions j 4%–5% in patients without adverse effects
j Resistance to activated protein C j 17%–20% those with predisposing condition
j Factor V leiden deficiency j 50% with two or more risk factors
j Protein C deficiency
j Protein S deficiency
j Antithrombin deficiency
j Hyperhomocysteinemia 11.20 Eosinophilia
Clinical evaluation
• Congenital heart disease and recent cardiac • Defined as increase in absolute eosinophils count
catheterization are important causes of arterial (AEC)
thrombosis • Moderate eosinophilia—elevation in AEC more than
• Limb edema, erythema and tenderness on 1500–5000 cells /micro L
dorsiflexion of foot (Homan sign) • Severe eosinophilia— > 5000 cells/micro L
174
mebooksfree.com
Causes of Eosinophilia
Acute Chronic
Allergic disorders Allergic disorders
• Asthma • Pemphigus
• Atopic dermatitis • Dermatitis herpetiformis
• Urticaria Auto immune disorders
• Drug hypersensitivity • Inflammatory bowel disease
Parasitic infections • Rheumatoid arthritis
• Toxocara Immunodeficiency syndrome
• Ascaris • Hyper IgE
• Amebiasis • Wiskott aldrich syndrome
• Strongyloidiasis • Omenn syndrome
• Toxoplasmosis • Graft versus host reaction
Fungal infections Myeloproliferative syndrome
• Bronchopulmonary apergillosis Hypereosinophilic syndrome
• Coccidiomycosis Loeffler syndrome
Malignancy Miscellaneous
• Hodgkin lymphoma • Thrombocytopenia with absent radii
• T cell lymphoma • Renal allograft rejection
• Acute myelogenous leukemia • Addison’s disease
• Myeloproliferative syndrome
• Hypereosinophilic syndrome

175
mebooksfree.com
Chapter | 12 |
Gastrointestinal System
and becomes projectile late in the course.

12.1 Idiopathic hypertrophic Baby would feel hungry and may want to feed
pyloric stenosis again. Constant hunger and poor weight gain
are characteristic. Persistent vomiting leads to
dehydration, electrolyte loss and ultimately results
• Occurrence in western countries is 1–3 per 1000 in hypokalemia, hyponatremia and hypochloremic
infants but uncommon in Asians. First born males metabolic alkalosis.
are affected with male female ratio of 5:1. Higher • Palpation of mass in transpyloric plane (Olive) is
incidence is seen in infants with B and O blood clinical hallmark of this condition. The mass is firm,
groups. freely mobile, approx. 2 cm in length, located in the
• Rarely associated with other congenital anomalies right upper quadrant of abdomen. Visible peristalsis
like trachea–esophageal fistula, hypoplasia of inferior from left hypochondrium to umbilicus may be seen
labial frenulum. (Fig. 12.1).
Etiology • Unconjugated Hyperbilirubinemia is commonly
• Exact cause is unknown associated clinical finding—Icteropyloric syndrome
• Can be associated with syndromes like eosinophilic • Constipation, failure to thrive and malnutrition are
gastroenteritis, Apert syndrome, Trisomy 18, Smith– seen if the diagnosis is delayed.
Lemli–Opitz syndrome and Zellweger syndrome Diagnosis
• Erythromycin given at first 2 weeks of life • Based on clinical history and mass palpation
Pathogenesis • Barium meal shows
• Factors like abnormal muscle innervation, j Elongated pyloric channel (string sign)
hypergastrinemia in infants, high levels of j Bulging of pyloric muscle into antrum (shoulder
prostaglandins and reduced level of nitric oxide sign)
might play a role in pathogenesis. j Narrowed channel with parallel streaks of barium
• Pyloric antrum muscles are hypertrophied and (double tract sign)
thickened. • Ultrasound shows dome shaped, thickened and
• Narrowed pylorus causes obstruction elongated pylorus. Pyloric length longer than
• Stomach distal to obstruction is dilated and 16 mm, pyloric muscle thickness greater than
hypertrophied 4 mm and pyloric diameter more than 14 mm are
Clinical features considered to be diagnostic. USG has a sensitivity of
∼95% in diagnosis of pyloric stenosis.
• Symptoms commonly occur anytime between
1–8 weeks of age but peak incidence at 3–4 weeks. • Electrolyte abnormality—Hypokalemic,
Preterms present 1–2 weeks late than term hypochloremic metabolic alkalosis with
babies. paradoxical aciduria.
• Nonbilious vomiting is the earliest presenting Treatment
symptom. Vomiting is initially nonprojectile but • Enteral Feeding should be stopped as soon as
progressive, occurs immediately after feeding the diagnosis is suspected. Dehydration and
176
mebooksfree.com
Gastrointestinal System Chapter | 12 |
• GERD is pathological if it causes reflux related

symptoms like irritability, retrosternal/epigastric pain
and pathological changes in esophagus
Pathogenesis
• Normal esophageal reflex is maintained by the tone
of lower esophageal sphincter (LES). Transient
LES relaxation (TLESR) is the basic mechanism
responsible for GER in most of the cases. TLESR is
defined as simultaneous relaxation of both LES and
surrounding crura.
• Other factors influencing the reflux are
j Obesity
j Hyperosmolar meals
j Sliding hernia
j Coughing/wheezing
Clinical features
• Reflux in Infants: Symptoms include recurrent
regurgitation with or without vomiting, weight loss
or poor weight gain and irritability, arching, choking,
gagging following feeds or refusal of feeds. Symptoms
manifest in first few months, peaks at 4 months
Figure 12.1 Visible gastric peristalsis.
and resolves by 1–2 years in all cases. Respiratory
presentations are common in the form of stridor and
wheeze
dyselectrolytemia should be corrected preoperatively. • Reflux in Older children: Presents with episodes of
Poorly corrected metabolic acidosis is associated with chest and abdominal pain following feeding. Some
risk of postoperative apnea. cases can present with feeding refusal and dystonic
• Ramstedt’s pyloromyotomy is the treatment of neck posturing (Sandifer syndrome). Chronic GERD
choice. This involves longitudinal division of can lead to asthma like exacerbations, laryngitis and
hypertrophied circular muscle bundles in pylorus, sinusitis.
without damaging mucosa. Surgical treatment is
curative. Rarely patients can have persistent symptoms
postsurgery due to incomplete pyloromyotomy or Symptoms Signs
other associated lesions like gastritis, GERD and
bowel atresia. Other surgical approaches include • Recurrent • Esophagitis
regurgitation with or • Esophageal stricture
laparoscopic pyloromytomy and endoscopic
without vomiting • Barrett esophagus
balloon dilatation.
• Weight loss or poor • Laryngeal/pharyngeal
• Oral or IV Atropine sulphate can be tried as weight gain inflammation
conservative therapy when surgical treatment is not • Irritability in infants • Recurrent pneumonia
available. It acts by relaxing pyloric muscles. • Ruminative behavior • Anemia
• Heartburn or chest • Dental erosion
pain • Feeding refusal
12.2 Gastroesophageal reflux • Hematemesis and Dystonic neck
• Dysphagia, posturing (Sandifer
disease (GERD) odynophagia syndrome)
• Wheezing, Stridor • Apnea spells
• GERD is the most common esophageal disorder • Cough, Hoarseness
in children. It occurs due to retrograde passage
of gastric contents into esophagus across the
lower esophageal sphincter. Gastroesophageal • High prevalence is seen with children with chronic
reflux (GER) is physiological and is seen in normal cough and asthma
infants. However, if GER is associated with clinical Diagnosis
symptoms and pathological changes, it is termed as • History and physical examination
GERD. • Barium study—has poor sensitivity and specificity
177
mebooksfree.com
• 24 hours oesophageal pH monitoring—high Causes of Acute Diarrhea

specificity but cannot detect non-acid reflux
• Endoscopy to diagnose erosive esophagitis and to Bacterial Viral
take biopsy from involved site. • Escherichia coli • Rotavirus - most
j Enterotoxigenic common
• Nuclear scintigraphy (99 mTc milk scan)—Not
j Enteropathogenic • Human calcivirus
a sensitive method to diagnose GERD. Presence
j Enteroinvasive • Enteric adenovirus
of milk in esophagus and lungs can be identified
j Enterohemorraghic • Cytomegalovirus
by the presence of radioactivity using gamma
j Enteroaggregative • Astrovirus
counter
• Shigella Parasitic
Treatment j S. sonnei • Giardia lamblia
• Physiologic GERD is a benign condition that requires j S. flexneri • Cryptosporidium parvum
life style modification. j S.dysentriae • Entamoeba histolytica
j Dietary modifications like concentrated, low • Vibiro cholerae • Cyclospora cayetanensis
volume, low osmolarity feeds. j O1 and O139 • Isospora belli
j Infants fed with head end elevation and in left • Salmonella • Balantidium coli
lateral position. j S. typhi
j Though prone position offers symptomatic relief, j S. paratyphi A,B,C
it should be avoided due to the risk of sudden • Campylobacter species

infant death syndrome. • Bacillus cereus
• Pharmacotherapy includes • Clostridium difficile
j Antacids—for acid neutralization • Clostridium perfringens
j H2 receptor antagonist—used as antisecretory • Staphylococcus aureus
agents
j Proton pump inhibitors—Omeprazole/
Pathogenesis
Lansoprazole
j Prokinetic agents
• Body has two fluid compartments—extracellular
(ECF) and intracellular (ICF)
• Extra esophageal manifestations of GERD needs more • ECF includes circulating blood, intestinal fluid and
aggressive treatment
secretions
• Surgery is indicated in refractory esophagitis • In diarrhea fluid loss comes from ECF which has high
and strictures and for those who have significant
sodium and low potassium
morbidity
• Loss of water leads to shrinkage of ECF with low
• Nissen’s fundoplication either by laparoscopic or sodium in turn causing low osmolality
endoscopic technique is the preferred surgery
• It allows leakage of water from ECF to ICF with
further shrinkage of ECF causing increased skin turgor
• As ECF is depleted, blood volume reduces resulting in
thready pulse and low blood pressure
12.3 Acute watery diarrhea • Low hydrostatic pressure causes reduction in filtration
of urine
Definition • Serum potassium levels falls as diarrheal stools
• Change in consistency and frequency of stools contain more potassium
• Liquid or watery stools occurring more than 3 times • Acidosis usually accompanies dehydration as
a day bicarbonate are lost in stools
• Without any visible blood Clinical features
• Persisting less than 14 days • Signs of Dehydration (Fig. 12.2a)
Etiology j Increased thirst and irritability
• Occurs through feco–oral route or by ingestion of j Sunken eyes
contaminated food and water j Dry tongue
• Risk factors includes j Depressed fontanelle if open
j Poor sanitation and personal hygiene j Delayed Skin pinch test
j Nonavailability of safe drinking water • Distended abdomen
j Unsafe food preparation practices • Passing urine at longer intervals
j Low socio economic status • Acidotic breathing
j Malnutrition • In severe cases thready pulse with low blood pressure
j Lack of exclusive breast feeding and reduced urine output
178
mebooksfree.com
Figure 12.2 (A) Signs of Dehydration. (B) Oral rehydration powder.
Evaluation • Amount fluid taken before and during illness

Goals of assessment • Medications and Immunization history
• To determine type of diarrhea Examination
• To look for dehydration • Assess dehydration status of the child
• To assess nutritional status • Features of malnutrition and systemic infections
• To rule out nondiarrheal illness
Lab investigations
• To assess feeding
• Hemogram
History
• Blood gas estimation
• Diarrhea—onset, duration and number of episodes • Serum electrolytes
per day
• Renal function test
• Associated with bloody stools • Stool microscopy
• Vomiting
• Presence of fever, cough or other symptoms
Assessment of dehydration status in diarrhea patients

General condition Well, alert Restless, irritable Lethargic, unconscious,
floppy
Eyes Normal Sunken Very sunken and dry
Tears Present Absent Absent
Mouth and tongue Moist Dry Very dry
Thirst Drinks normally, not Thirsty, drinks eagerly Drinks poorly or not able
thirsty to drink
Skin pinch Goes back quickly Goes back slowly Goes back very slowly
Dehydration status The patient has no signs If patient has 2 or more If patient has 2 or more
of dehydration signs, there is some signs, there is severe
dehydration dehydration
Treatment Plan A Plan B Plan C
Principles of management Oral rehydration therapy (ORT)

1. Rehydration and maintaining good hydration • ORT has revolutionized the management of diarrhea
2. Ensure adequate feeding • ORT (Fig. 12.2b) includes
3. Oral supplementation of zinc and probiotics j ORS solution of recommended composition
4. Early recognition of danger signs and treatment of j Solution made from sugar and salt (if prepared
complications correctly)
179
mebooksfree.com
j Food based solutions with appropriate j If ORT is not successful then treat as severe
concentration of salt, like rice kanji, butter milk, etc. dehydration
Plain water given along with continued feeding
Treatment Plan C
j
• Option for children with severe dehydration

Composition of ‘Low Osmolarity ORS’ • Objective is to rehydrate the child with intravenous
fluids
Constituent g/dL Osmole or ion mmol/L
• Ringer lactate is preferred solution and alternative is
Sodium chloride 2.6 Sodium 75 normal saline
Glucose, 13.5 Chloride 65 • Total of 100 mL/kg of fluid is given
anhydrous j Infants < 1 year—30 mL/kg body weight within
Potassium 1.5 Glucose 75 first 1 hour, followed by 70 mL/kg body weight
chloride anhydrous over next 5 hours
j Older children > 1 year—30 mL/kg body weight
Trisodium 2.9 Potassium 20
within half an hour, followed by 70 mL/kg body
citrate
weight over next 2.5 hours
Citrate 10 • Child should monitored every 15–30 min for pulses,
Total osmolarity 245 blood pressure, urine output and hydration status
• After bolus the child should be reassessed
• Low osmolarity ORS causes reduction of stool j Persistence of dehydration—intravenous infusion
output, decreases vomiting and decrease in use of is repeated
intravenous fluid without causing hyponatremia j Hydration improved but some dehydration is
• Currently low osmolarity ORS is recommended for all present—discontinue iv fluids, ORS given as in plan B
types of diarrhea and for all age groups j No dehydration—discontinue iv fluids, treatment
plan A is followed
Treatment Plan A
• Treatment of no dehydration Nutritional management of diarrhea
• Can be treated at home after explanation of feeding • Early feeding during acute diarrhea reduces stool
and danger signs volume and prevents malnutrition
• The mother/caretaker is advised to • Breastfeeding should be continued in exclusively
j Give more fluids than normal breastfed babies as it helps in better weight gain and
j Continue feeding/breastfeeds decreases risk of persistent diarrhea
j Bring the child back after 3 days, or earlier if • Optimal energy dense food with least bulk is given
he has any of the danger signs diarrhea beyond in small quantities and frequently
3 days, increased volume/frequency of stools, • Fiber rich diet should be avoided
repeated vomiting, increasing thirst, refusal to • In nonbreastfed babies cow or buffalo milk should
feed, fever or blood in stools be given undiluted after dehydration correction
Treatment Plan B • During recovery, at least 125% of RDA of nutrients
should be supplemented
• Given for child with some dehydration
• Objective is to treat dehydration, electrolyte • Zinc supplementation is part of diarrhea therapy
abnormalities and continue feeding • Zinc is given as sulphate or acetate or gluconate at a
dose of 20 mg/kg/day for children > 6 months and
• Fluid requirement is calculated as follows
10 mg/kg for infants < 6 months for 14 days.
j Providing daily requirement of fluid
j Rehydration to correct the water and electrolyte Drug therapy
deficits • Acute Diarrhea are self-limiting in most of the cases
j Maintenance of fluids and replacement of and does not require any routine antibiotics
ongoing loss • Antibiotics are, however, recommended in bacillary
• Daily requirement dysentery, cholera, amebiasis and giardiasis
j Upto 10 kg—100 mL/kg • Malnourished children, diarrhea as part of systemic
j For next 10—20 kg—50 mL/kg infection, young infants and those who show
j > 20 kg—20 mL/kg significant signs of sepsis should be treated with
• Deficit replacement systemic antibiotics
j 75 mL/kg of ORS given over 4 hours and child is • Antimotility drugs should be avoided
reassessed after that • Antisecretory agents like Racecadotril exerts its effect
j Dehydration is present—give another treatment by inhibiting intestinal enkepalinase
with ORS • Probiotics are proposed as adjunctive therapy in
j No dehydration—treat as no dehydration plan diarrhea treatment. Common organisms used are
180
mebooksfree.com
Lactobacillus, Bifidobacterium, Saccharomyces Amebic dysentery

boulardii etc • Less common in children
Complications • Onset is insidious
• Electrolyte Imbalance • Presents with blood in stools with abdominal pain
j Hypernatermia • Tinidazole or metronidazole is the drug of choice
j Hyponatermia
j Hypokalemia
j Hypoglycemia 12.5 Persistent diarrhea
• Metabolic acidosis
• Acute renal failure Definition
• Hemolytic uraemic syndrome • Diarrheal illness with passage of three or more loose
Prevention stools of presumed infectious etiology
• Promotion of exclusive breastfeeding up to 6 months • Starting acutely and lasting for more than 14 days
of age
Etiopathogenesis
• Improved complementary feeding practices • Persistent diarrhea starts as acute infection but
• Use of clean drinking water prolongation is not due to infection
• Three C’s—Clean hands, Clean container, Clean • More common in malnourished children
environment
• Common cause include
• Use of sanitary toilets j Malabsorption of carbohydrates and fats
• Safe disposal of the stool of young children j Dietary protein allergy and intolerance
• Rota virus vaccination j Intestinal parasitosis
j Persistent infection with one or more enteric
pathogens
12.4 Dysentery
• Various factors are implicated in pathogenesis
j Predominant problem is worsening nutritional
• Presence of grossly visible blood or mucus in stools status, which in turn impairs the reparative process
• Consequence of infection by bacteria or amoeba leading to poor absorption of nutrients
• Bacillary dysentery is more common than amebic j Poor calorie intake due to anorexia, faulty
dysentery in children feeding, improper counseling leading to further
Bacillary dysentery malnutrition
Causative organism j Secondary lactose intolerance
Impaired absorption of carbohydrates due to
• Shigella species—S. dysentreriae, S. flexneri, S. sonnei,
j
damage to the upper small intestinal mucosal

S. boydii
absorptive surface
• Enteroinvasive and Enterohemorraghic E.coli
Food intolerance/allergy develops due to loss of
• Salmonella
j
brush border enzymes and direct macronutrient

• Campylobacter jejuni
absorption
• Yersina enterocolitica
j Pathogenic E.coli and enteroaggresive E.coli can
Clinical features result in malabsorption
• Presents with fever and diarrhea j Associated urinary tract infection
• Diarrhea is initially watery followed by blood and j Cow’s milk allergy
mucus mixed with stools j Use of antibiotics can suppress gut flora
• Tenesmus and abdominal pain can lead to bacterial overgrowth and altered
Investigations intestinal flora
• Haemogram j Cryptosporidium can cause persistent diarrhea
• Stool microscopy even in immunocompetent patients
• Stool culture Clinical features
Treatment • Well hydrated in spite of loose stools
• Administration of ORS • Three forms of persistent diarrhea are observed
• Zinc supplementation/Probiotics j Mild forms—several loose stools/day without
• Continuation of oral diet significant weight loss and dehydration , can be
• Antibiotics managed on outpatient basis
j Oral Co-trimoxazole/ciprofloxcin/cefixime in j Moderate form—several loose stools/day with
stable patients marginal weight loss without dehydration and
j IV ceftriaxone for sick children intolerance to milk and milk products
181
mebooksfree.com
j Severe form—life threatening and have weight Correction of dehydration, electrolytes and
j
loss, dehydration and with secondary infection. hypoglycemia

Need hospital admission j Evaluation for infection and their management
• Explosive stools in presence of secondary lactose j Nutritional therapy
intolerance • Children requiring hospital admission
• Major consequences are growth failure, worsening j Age less than 4 months and not breastfed
malnutrition and death j Presence of dehydration
• Stool pH is low and stool for reducing substance is j Severe malnutrition
positive j Presence of systemic infection
Management
• Principles of management are
Diets for Persistent diarrhea
Plan A (Reduced lactose) Plan B (Lactose free) Plan C (Monosaccharide based)

Ingredient Amount (g) Ingredient Amount (g) Ingredient Amount/L
Puffed rice 12.5 Puffed rice 13.5 Chicken 100 g
Milk 40.0 Egg 11.0 Glucose 20–40 g
Sugar 2.25 Sugar/Glucose 3.5 Coconut oil 40–50 g
Oil 2.0 Oil 3.5 KCL (15%) 7.5 mL
Water to make 100.0 Water to make 100.0 NaHCO3 20–30 mL
(7.5%)
Total 1000 mL
The above will yield following: The above will yield following: The above will yield energy 720 Kcal
Energy density 96 Kcal/100 g Energy density: 92.2 Kcal/100 g and protein 26 g
Protein 10.0% Protein: 9.5%
Carbohydrate 55.87% Carbohydrate: 56.9%
Lactose 1.73% Fat: 33.29%
Fat 33.9% Amino acid score: 1.0%
Amino acid score 1.0%
Note: Note: Note:
• Puffed rice is ground and • Egg white is added to the mixture • It is prepared by grinding the
appropriate quantities are mixed of weighed rice, sugar and oil. precooked boneless chicken stuff
with sugar and oil. • Boiled water is added to make a in a mixer.
• Boiled water is then added to thick gruel weighing 100 g • Glucose, oil and some water are
make a thick gruel. added to it and is brought to a
• This feed has a shelf life of boil.
around 3 hours • Additional water is added to
make a final volume of 1 liter.
• Finally KCl and NaHCO3 are
added to safeguard against
spoilage and it is stored in a
refrigerator.
• Glucose is initially added in 2%
concentration and then built up
to 4% by increasing 1% every
alternate day.
• To reduce osmolar load a mixture
of glucose and sugar may be
employed.
• Any vegetable oil can be used in
place of coconut oil.
182
mebooksfree.com
Nutrition Resumption of diet after discharge

• Feeding should be started as early as possible • Milk free diet should be given for 10 days
• Daily calorie intake 100 kcal/kg/day in 6–7 feeds • After 10 days milk can be introduced and continued if
initially they show no signs of lactose intolerance
• Increase the calorie intake to 150 kcal/kg/day over • Age appropriate diet can resumed after 1 week
1–2 weeks Supplementation of vitamins and minerals
Initial diet A • Vitamins and minerals are given at twice the RDA
• Reduce lactose diet • Iron should be started only after diarrhea has ceased
• For children with secondary lactose intolerance • Vitamin A (single dose) and zinc are supplemented
• Reducing lactose to not more than 2 g/kg/day in to enhance the recovery
children fed entirely on animal milk • Magnesium and potassium are given to severely
malnourished children for 2 weeks
Second diet B
• Lactose free diet with reduced starch Antibiotics
• Used in children who do not respond to diet A and if • Indiscriminate use of antibiotics is one of the cause
they are free of infection for persistent diarrhea
• Milk protein replaced by chicken, egg or protein • Antibiotics are reserved in
hydolysate j Severe malnutrition
j Evidence of systemic infection
Third diet C
j Very young infants (<3 months)
• Monasaccharide based diet j Combination of Cephalosporin and
• Indicated in children who don’t tolerate cereal in diet aminoglycoside can be started
B and shows no weight gain for diet A or B
• Contains glucose and protein source as egg white or Prevention
chicken • Promotion of exclusive breastfeeding
• Active and prompt treatment of diarrhea
Indication to change diet
• Judicious use of antibiotics in treatment of diarrhea
• Marked increase in stool frequency • Avoiding predisposing factors like bottle feeding,
• Features of dehydration after 48 h. of initiating the malnutrition and use of banned drugs
diet
• Failure to gain weight by day 7 in absence of
symptoms/infection 12.6 Chronic diarrhea
Indication for total parenteral nutrition
• Protracted diarrhea with recurrent dehydration • Diarrhea more than 2 weeks of duration
• Intolerance to plan C treatment • Onset is insidious
• No weight gain/weight loss even after plan C diet • Not associated with infectious cause
Causes
Age < 6 months Age >6 months to 5 years Age > 5 years

• Cow milk protein allergy • Cow milk protein allergy • Celiac disease
• Lymphangiectasia • Celiac disease • Giardiasis
• Urinary tract infection • Giardiasis • Gastrointestinal TB
• Short bowel syndrome • Toddlers diarrhea • Inflammatory bowel disease
• Immunodeficiency states • Lymphangiectasia • Immunodeficiency
• Cystic fibrosis • Short bowel syndrome • Bacterial overgrowth
• Anatomical defects • Tuberculosis • Lymphangiectasia
• Inflammatory bowel disease • Tropical sprue
• Pancreatic insufficiency
Pathophysiology • Secretory diarrhea—exotoxins cause increase in

• Results from breakdown of intraluminal factors intracellular AMP/GMP resulting in increased fluid
responsible for digestion and mucosal factors and sodium secretion
responsible for digestion and secretion • Mutation in apical membrane transport protein
• Osmotic diarrhea—increased osmotic load is due to • Alteration in intestinal motility cause secretory diarrhea
undigested nutrients which gets fragmented into • Inflammatory process like IBD can cause chronic
short chain fatty acids diarrhea
183
mebooksfree.com
Approach • Nitazoxanide therapy can be instituted where Giardia

• Age of onset lamblia or Cryptosporidium parvum are suspected or
• Small bowel or large bowel type found
j Large volume diarrhea without blood and
mucus—small bowel type
j Small volume with blood and mucus—large bowel
type 12.7 Intussusception
• Gastrointestinal Vs systemic cause
j Mostly diarrhea are of intestinal origin • Defined as telescoping of proximal segment
j Can also be due to pancreatic and hepatobiliary (intussusceptum) of intestine into a distal segment
causes (intussuscipiens) of intestine
• Specific questions in history • Can be ileocolic, colocolic, or ileoileal types
j Duration of symptoms, nature, frequency, • It is most common cause of intestinal obstruction in
consistency 5 months to 3 years of age
j Age of onset and its relationship with dietary changes • Incidence in 1-4 in 1000 live birth
j Family history of atopy • Male female ratio is 3:1
j History of abdominal surgery, drug intake and
medical conditions predisposing to diarrhea
Evaluation
Evaluation of patient with chronic diarrhea

Phase I • Clinical history—Urine output, fluid
intake
• Physical exam
• Nutritional evaluation
• Stool exam (pH, reducing substances,
pus cells, fat, ova and parasites)
• Stool culture
• Stool for toxin identification
• Hemogram, ESR, electrolytes, urea and
creatinine
Phase II • Sweat chloride
• 72-hour stool collection for fat
determination
• Stool electrolytes, osmolality Etiology
• Stool for phenolphthalein, magnesium • Predisposed by new food during weaning period
sulfate, phosphate, breath H2 test • Vaccination—Rotavirus vaccine
Phase III • Endoscopy • Upper respiratory tract infection—adenovirus C
• Small intestinal biopsy • Infants less than one year of age are at high risk
• Sigmoidoscopy • Henoch schonlein purpura, ITP, hemophilia, cystic
• Colonoscopy fibrosis, celiac disease and Crohn disease are other
• Contrast studies risk factors
Phase IV • Hormonal assay: vasoactive intestinal Pathology
polypeptide, 5-hydroxyindoleacetic • The most common site—ileocecal region
acid, gastrin and secretin • The most common lead point—a hypertrophied
Peyer’s patch
Treatment • Other lead points are meckel’s diverticulum, intestinal
• Treatment depends on the cause polyp, neurofibroma, intestinal duplication cysts
• Restriction of carbonated drinks or excess fruit juice hemangioma and malignant conditions such as
will reduce stool frequency in nonspecific chronic lymphoma, or Kaposi sarcoma
diarrhea • Constriction of mesentery and venous congestion
• Secondary carbohydrate intolerance—reduction of in the innermost layer of intussusception will lead
lactose or sucrose in the diet will be helpful to bloody stools with mucus (red currant jelly
• Lifelong Gluten free diet in celiac disease stool)
• Correction of iron, folate and other vitamin/mineral • This leads to bowel ischemia, necrosis, intestinal
deficiencies by supplementation gangrene and shock
184
mebooksfree.com
Clinical features • Defects in epithelization and recanalization of

• Classical cases present with episodes of incessant developing ducts
cry and drawing up of the legs. These episodes last • Congenital weakness of duct wall
for few minutes and recur repeatedly. Passage of
Types of choledochal cyst
stool may be normal during initial stages but mixed
with blood and mucus later (the ‘red currant jelly’ Type 1 Commonest 80%–90%. Fusiform
stool) dilatation of whole or a part of CBD.
• Preschool and older children complain of severe Intra hepatic ducts are normal
paroxysmal colicky abdominal pain. Type 2 Diverticulum that projects out CBD.
• Sausage-shaped abdominal mass may be palpable in Progressively enlarges and compresses
right upper quadrant in some cases. CBD
• Emptiness in the right iliac fossa—The sign of Dance Type 3 Choledochocele. Dilatation of intra
• Bilious vomiting is seen in late presentations duodenal part of CBD where the
• Cases presenting late show features of septicemia and pancreatic duct joins CBD
peritonitis
Type 4 Multiple focal dilatation of intra and
Diagnosis extra hepatic biliary tree
• X ray shows paucity of air in right lower quadrant Type 5 Caroli disease. Focal dilatation of intra
• Ultrasound confirms diagnosis—doughnut sign hepatic biliary system
• Doppler is used to assess vascularity of bowel
• Barium enema shows claw sign
Treatment Clinical features
• General measures • Diagnosed during infancy
j Resuscitation with intravenous fluids, • Triad
j Broad-spectrum antibiotics j Abdominal mass
j Naso-gastric drainage j Abdominal pain
• Nonoperative reduction j Jaundice
j Cases presenting within 24 h—Hydrostatic • Cholestatic jaundice
reduction under ultrasound guidance • Severe liver dysfunction
j Contraindications include perforation, peritonitis • Features of acute cholangitis
and shock Diagnosis
• Surgical reduction • Ultrasonography
j If nonoperative reduction fails, exploratory • Magnetic resonance cholangiopancreatography
laparotomy is treatment of choice (MRCP) is useful for preoperative assessment
j If needed, resection and anastomosis of bowel Treatment
must be done
• Primary excision of the cyst
Prognosis • Roux en-Y choledochojejunostomy
• Untreated intussusception usually fatal in infants
• Recurrence rate after reduction is approximately 10%
and after surgical reduction is 2%–5%
• Recurrence usually occurs within 72 hours 12.9 Malabsorption
• Defined as failure of absorption of one or more

nutrients
12.8 Choledochal cyst • Divided into two categories
j Impaired breakdown of nutrients
• Congenital dilatation of common bile duct j Defective mucosal uptake and transfer of nutrients
• Can cause progressive biliary obstruction and biliary Etiology
cirrhosis
• Celiac disease ( most common)
• Can involve both intra and extra hepatic biliary • Cystic fibrosis
radicals
• Immunodeficiency
Pathogenesis • Infection
• Exact pathogenesis is unknown j Giardia
• At the junction of CBD and the pancreatic duct, j Cryptosporidium
pancreatic enzymes enters into CBD causing • Cow milk allergy in less than 3 years
inflammation, weakness and dilation of the duct • Inflammatory bowel disease
185
mebooksfree.com
Clinical features Management

• Chronic diarrhea • Treating the underlying cause
• Short stature • Supplementation with iron, folic acid, multivitamins
• Anemia and calcium
• Rickets • Treat the infection
• Constipation j Metronidazole for giardia
Approach j Nitazoxanide for cryptosporidium
• Clinical suspicion of MAS based on history and • Cow’s milk and milk products are avoided in cow’s
physical examination milk protein allergy
• Confirmation by laboratory investigations • Gluten free diet in celiac disease
j Complete hemogram shows anemia,
thrombocytosis (celiac disease), acanthocytes
Stool pH for reducing substance
12.10 Inflammatory bowel disease
j
j Fecal fat estimation, D-xylose excretion test,

lactose hydrogen breathe test, Schilling test
• Finding out the cause by endoscopy, mucosal biopsy, • Distinguished into two groups—Ulcerative colitis and
imaging Crohn’s disease (Table 12.10)
Table 12.10 Characteristic features of Ulcerative Colitis and Crohn disease
Ulcerative colitis Crohn’s disease

Distribution Begins in rectum and extends Can involve any part of alimentary
proximally to variable distance tract from mouth to anus
Age group 10–—11 years 10–—11 years
Clinical features Common Less common
Bloody stools
Abdominal pain Less common Common
Systemic signs and symptoms Less common More common
Growth failure/anorexia Less common Common
Peri-anal disease Abscess, fistula are formed Present
Extra intestinal manifestations Sclerosing cholangitis Oral aphthous ulcers
Pyoderma gangrenosum Peripheral arthritis
Ankylosing spondylitis Erythema nodosum
Chronic active hepatitis Episcleritis
Gall stones and renal stones
Diagnosis Perinuclear anti neutrophilic Anti sacchromyces cerevisae
Serology cytoplasmic antibody (pANCA) positive antibody(ASCA) positive
Endoscopy Granularity, loss of vascular pattern, Deep irregular serpiginous/
friability, diffuse ulceration aphthous ulcer with normal
intervening mucosa (skip lesions)
Histopathology Mucosal disease with cryptitis, crypt Transmural inflammation with
distortion, crypt abscess, goblet cell non caseating granuloma
depletion
Treatment Sulfasalazine 5-aminosalicylate
Medical Steroids Steroids
Azathioprine, 6-mercaptopurine Azathioprine, 6-mercaptopurine
Surgery Total colectomy/combine colectomy Remove as limited length of bowel
with an endorectal pull-through as possible
Prognosis Intermittent flare-up common Remission and exacerbation more
common. Risk of colon cancer is
high
186
mebooksfree.com
j A congenital discontinuity of duodenum in the

region of ampulla of Vater
j Incidence: 1 in 6000 live births
j More commonly associated with Down’s
syndrome (30%).
• Clinical Features
j Antenatal history of polyhydramnios
j Look for facial dysmorphism of Down’s syndrome
and other anomalies of trisomy 21
j Bilious vomiting within hours of birth
j Distended stomach and duodenum
j Visible gastric peristalsis.
• Investigations
j X-ray abdomen: Double bubble sign of gas
distending stomach and duodenum
Figure 12.3 Gastroschisis. j Biochemical test: Serum electrolytes, karyotype
study, if signs of trisomy 21.
• Management
12.11 Gastroschisis j Stop enteral feeding and start IV maintenance
j Insert NG tube, aspirate hourly
Correction of electrolyte and acid base
• Abdominal viscera, including stomach, small bowel,
j
disturbance
colon, ovaries/testis prolapse through a congenital
j Surgical Management
defect on the right side of umbilicus.
j Early definitive surgical treatment is required by
Epidemiology and Pathogenesis anastomosis of healthy duodenal segment.
• Incidence of 1 in 7000 live births • Prognosis
• Occurs equally in males and females j Usually good, unless associated with other medical
• Association with young maternal age problems.
• The bowel is eviscerated and not covered by a sac
Clinical Features
• Most cases are identified by antenatal USD 12.13 Exomphalos (Omphalocele)
• There is no sac covering the gut (Fig. 12.3)
• Appearance varies with normal looking gut to be
covered in thick fibrin like shell. • It is a congenital umbilical defect with prolapse of gut
Management within an amniotic sac outside the abdominal cavity
• Immediate: (Fig. 12.4)
j Cover the exposed bowel with cellophane or
preformed plastic sheath
j Insert NG tube, aspirate frequently and leave on
free drainage
j Baby is kept ‘nil per oral’—Nothing by mouth
j Start IV maintenance fluids
j Start IV antibiotics
j Monitor and correct dyselectrolytemia.
• Surgery:
j The defect requires surgical closure as early as
possible.
Outcome
• 90% survival
• Necrotizing enterocolitis (NEC) as a complication
12.12 Duodenal Atresia
• Etiopathogenesis Figure 12.4 Omphalocele.
187
mebooksfree.com
Epidemiology • Types—According to length affected

• Incidence: 1 in 5000 live births j Short segment disease (7%): Rectal and sigmoid
• Occurs equally in males and females colon
• Associated condition: j Intermediate segment disease (15%): Extend up to
j Beckwith–Wiedemann syndrome transverse colon
j Trisomy 13, 18, and 21 j Long segment disease (8%–10%): Enter colon and
j 40% will have other congenital defects. terminal part of ileum.
• Two types of exomphalos depending on size. Clinical features
Exomphalos major: defect more than 5 cm diameter
j
• Usually diagnosed in neonatal period. Common
j Exomphalos minor: Defect less than features include failure to pass meconium in first
5 mm diameter. 48 hours of life, abdominal distension, bilious or
Management nonbilious vomiting, gastric aspirates and feeding
• Nothing by mouth intolerance. Progressively worsening constipation
• Insert NG tube and abdominal distension is seen beyond neonatal
• IV maintanence fluids period.
• Monitor blood glucose for hypoglycemia • Hirschsprung enterocolitis—Progressive
• Upper GI contrast study dilatation of bowel proximal to obstruction
• Echocardiography and karyotyping leads to increased intraluminal pressure and
• Surgical Treatment decreased blood flow and disruption of mucosal
j Closure of the defect in one or more steps. barrier. Stasis of stools leads to bacterial growth
Prognosis (Clostridium difficile, Satphylococcus aureus) can
• Prognosis depends on associated malformations present with fever, foul smelling diarrhea and signs
of bowel obstruction
• Older children present with long standing
constipation with the onset since birth. Examination
often reveals distended, tympanitic abdomen with
12.14 Hirschsprung disease palpable fecal masses.
(congenital aganglionic megacolon) • Protein losing enteropathy leading on to
hypoproteinemia and failure to thrive is rarely seen.
• Developmental disorder of enteric nervous system. • Can be associated with
Failure of migration of neural crest cells down the gut j Trisomy 21
during embryogenesis. j Anorectal abnormalities
• Characterized by absence of ganglionic cells in j MEN syndrome
submucosal and myentric plexuses of distal Differential diagnosis
intestine • Meconium plug syndrome
• Most common cause of lower intestinal obstruction • Hypothyroidism
in neonates • Small left colon syndrome (diabetic mother)
• Incidence is 1 in 500 live births • Distal small bowel/Colonic atresia
• Male preponderance with ratio of 4:1 • Meconium ileus—Cystic fibrosis complex
• Associated with Down’s syndrome, Waardenburg’s Investigations
syndrome.
• Plain X ray abdomen –
Pathogenesis j Bowel distension with multiple air fluid levels
• Ganglion cells of neural crest migrate till the j Absence of rectal gas
proximal anal canal then into myentric plexus and j In enterocolitis—Bowel wall thickening, mucosal
submucous plexus. These cells uses nitric oxide as irregularity with fluid levels.
neurotransmitter for coordinated peristalsis of bowel • Barium enema—narrow aganglionic segment
• In Hirschsprung’s, absence of neural innervation (Transition zone) with proximally distended
leads to arrest of neuroblast migration from the bowel
proximal to distal bowel. Absence of myenteric and • Anorectal manometry in older children—which
submucosal plexus, results in inadequate relaxation measures the pressure in the internal anal sphincter.
of the bowel wall and bowel wall hypertonicity. • Suction Rectal biopsy is gold standard investigation –
Intestinal obstruction occurs due to uncoordinated j Site of biopsy is 2 cm above anal canal
bowel peristalsis. j Absence of ganglion cells in the submucosa
• Aganglionosis can be restricted to rectosigmoid in j Hypertrophied nerve bundles in aganglionic
80% and long segment disease in 10%–15 % segment that are stained with Acetylcholinestrase
188
mebooksfree.com
Treatment • (VACTERL) association consists of Vertebral defects,

• Surgery is only treatment of choice. Three-stage Anal atresia, Cardiac defects, Tracheo-esophageal
Surgery is done fistula, Renal and Limb anomalies.
j Stage 1: Initially temporary colostomy is Types
preformed to relieve obstruction before definitive
• Low Variety
surgery. Biopsies are done to confirm the site of j Rectum terminates close to perineal skin
transition zone j Imperforate anus, rectal stenosis
j Stage 2: Pull through procedure done to j Anterior anus in girls.
anastomose ganglionic colon and anus
• High Variety
j Stage 3: Closure of colostomy. j Rectum terminates in pelvis
• Currently primary pull through surgery is preferred, if j Anal stenosis, anal membrane, perineal fistula,
there is no associated complication rectourethral fistula in boys, retrovestibular in girls,
• Three surgical procedures are available—Swenson, retrovesicular fistula, cloacal malformations
Duhamel, and Soave - boley
Examination
Prognosis
• In Male
• 75% will achieve good bowel control by adulthood j No anal opening (Fig. 12.5a)
• Complications, which may occur, include fecal j Opening on perineum
incontinence, constipation and enterocolitis. j Meconium may be seen running subcutaneously
• May have protracted course if associated with Down’s along the raphe of midline.
syndrome
• In Female
j Anterior anus most common presentation
j Rectovestibular fistula.
12.15 Anorectal Anomalies Investigations
• X-ray pelvis in lateral prone
Introduction j Taken 24 hours of birth with pelvis tilted up and
• Anorectal anomalies consist of wide range of defects radiopaque marker placed over anal dimple. It
with variable severity. reveals the position of rectal gas. Short distance
• Epidemiology between rectal gas shadow and anal marker
j Incidence: 1 in 5000 live births • Invertogram (Fig. 12.5b)—Coin or any other
j About a half will have another anomaly radiopaque material placed over the anticipated
j Vertebral, anal, cardiac tracheal, esophageal, renal, anal opening site and the infant is held upside
limb down
Figure 12.5 (A) Absent anal opening; (B) Invertogram.
189
mebooksfree.com
j Interpreted based on the distance between distal Prognosis

gas shadow in rectum and the coin • Constipation
– Distance >2 cm indicates high Variety • Constipation with fecal incontinence, particularly in
– Distance <2 cm indicates low Variety high variety.
• Fluoroscopy contrast study—To rule out associated
fistula
• Ultrasound
Management 12.16 Approach to a Child with
• Low Variety upper gastrointestinal bleeding
• Anal dilatation followed by anoplasty in newborn
period.
• High Variety • Defined as overt or occult bleeding from source
j Initial defunctioning colostomy proximal to the proximal to ligament of treitz (esophagus, stomach,
defect. or duodenum proximal to the duodenojejunal
j Definitive surgical intervention few months later junction)
with posterior sagittal anorectoplasty. Causes
Newborn Infant Children

• Swallowed maternal blood • Stress ulcer/gastritis • Mallory–Weiss tear
• Hemorrhagic disease of • Acid-peptic disease • GERD/Acid-peptic disease
newborn • Mallory–Weiss tear • Varices
• Stress gastritis • Vascular anomaly • Stress ulcer/erosive gastritis
• Cow’s milk protein allergy • Duplication cyst • Caustic injury
• Acid peptic disease • Varices • Foreign body
• Vascular anomaly • Webs • Vasculitis
• Coagulopathy • Intestinal obstruction • Crohn’s disease
• Intestinal obstruction
• Dieulafoy lesion
• Hemobilia
• Pancreatic pseudoaneurysm
Evaluation of Upper GI bleed Management

• Vital signs are recorded—pulse rate and blood • General supportive measures
pressure • Achieving hemodynamic stability and correction of
• Monitor urine output, fluid intake, shock and mental hypovolemic shock
status • Oxygen supplementation for hypoxia due to blood
• Hyperventilation is early sign of acidosis loss
• Nasogastric aspirations can confirm the bleeding from • Blood transfusion should be given if hemoglobin less
upper GI sources than 8 gm/dl
Clinical clues to etiology are listed in table • Antibiotics are given to reduce bacterial infection and
variceal rebleeding
Mallory-Weiss tear Emesis before hematemesis,
Specific therapy
pain
Variceal bleeding
Esophageal ulcer Odynophagia, GERD, H/O pill • Drugs used to reduce the bleeding
ingestion j Vasopressin—reduces the portal pressure by
Stress gastritis/ Sick patient in ICU, respiratory causing splanchnic arterial vasoconstriction
Peptic Ulcer failure/NSAID ingestion/pain j Telepressin—synthetic analog of vasopressin
Angiodysplasia Renal failure, hereditary j Somatostatin—acts by inhibiting the vasodilatory
hemorrhagic telangiectasia hormones release
Aortoenteric fistula H/O aortic aneurysm or surgery j Octreotide—synthetic analog of somatostatin with
less half life
Variceal bleed Significant, painless,
splenomegaly, jaundice, • Balloon tamponade
stigmata of chronic liver • Endoscopic variceal ligation/sclerotherapy
disease, ascites • Transjugular intrahepatic portosystemic shunt
• Surgery
190
mebooksfree.com
Non variceal bleeding • Presence of hard stools with difficult defecation—anal

• Depends on the source of bleeding fissure
• Various diagnostic modalities are employed to find • History of constipation, straining at stools, digital
out the source evacuation—solitary rectal ulcer syndrome
• Treatment options are H2 receptor antagonists/ • Red currant jelly stools—intussusception
PPIs, vasoactive agents, endotherapy including • Presence of anal fissure and tags—crohn’s disease
electrothermal agents such as endoclips and argon • Palpable purpura with abdominal pain—henoch
plasma coagulation schonlein purpura
Investigations
• Hemogram, ESR, prothrombin time
12.17 Approach to a child with • Stool examination
• Colonoscopy
lower gastrointestinal bleeding • Ultrasonography of abdomen
• 99m Tc pertechnate scan
• Bleeding occurs from the site distal to ligament of • Triple phase CT angiography
Treitz (distal to the duodenojejunal junction) • Endoscopy
Causes Treatment
• Anal fissure—Treatment of constipation,
Neonate Children > 2 yr laxatives, Sitz bath, topical 0.2% glyceryl nitrate
Colitis twice daily
• Solitary rectal ulcer syndrome—Sucralfate enema,
• Infectious colitis • Infectious colitis twice daily, for 3–6 weeks with training on “not to
• Cow milk protein • Inflammatory bowel
strain during defecation” and YAG laser treatment for
allergy disease
severe bleeds
• Necrotising • Tuberculosis
enterocolitis • Pseudomembranous • Hemorrhagic infective colitis—Antimicrobials
• Hirschsprung colitis • Polyps—Colonoscopic snare polypectomy
enterocolitis • Cow milk protein allergy • Inflammatory bowel disease and ulcerative colitis—5
• Systemic vasculitis amino-salicylic acid, steroids, cyclosporine, total
colectomy
Non colitic
• Crohn’s disease: Steroids, azathioprine,
• Anal fissure • Fissure infliximab,metronidazole and ciprofloxacin
• Intussusception • Polyposis syndrome • Vascular lesions—Therapeutic endoscopy
• Duplication cyst • Solitary rectal ulcer
• Portal colopathy and variceal bleed—Octreotide,
• AV malformation syndrome
transjugular intrahepatic portosystemic stent shunt
• Rectal prolapse • Meckel’s diverticulum
and shunt surgery
• Meckel’s • NSAID induced ulcer
diverticulum • Hemorrhoids
• Hemorraghic • Henoch schonlein
disease of newborn purpura
• Coagulopathy • AV malformation
12.18 Liver abscess
• Coagulopathy
• Pyogenic liver abscess is more common than amebic
Approach to diagnosis liver abscess
• Increased frequency of stool mixed with blood and Causes
mucus associated with crampy abdominal pain— • Infection reaches the liver by following routes
infectious colitis j Portal vein
• Sick preterm with abdominal distension, blood in j Biliary tree obstruction and cholangitis
stools, feed intolerance and systemic instability— j Systemic sepsis
necrotising enterocolitis j Direct inoculation
• Delayed passage of meconium with constipation, • Children on immunosuppressive drugs or with
abdominal pain—Hirschsprung disease defects of neutrophil function are at increased risk
• Allgeric colitis—seen in infants fed with cow’s milk • Staphlococcus aureus are common organism
• Onset of bloody diarrhea after antibiotics use— • Invasive intestinal amebiasis can lead to amebic liver
pseudomembranous colitis abscess
• Presence of extraintestinal signs like aphthous ulcer, Clinical features
iritis—inflammatory bowel disease • Pyogenic abscess involve right lobe of liver
191
mebooksfree.com
• Amebic abscess is solitary whereas pyogenic may be Clinical features

multiple • Prodromal symptoms are low grade fever, malaise,
• Fever anorexia
• Right upper quadrant pain • Vomiting
• Jaundice is uncommon • Jaundice
• Examination shows tender hepatomegaly • Examination shows icterus, hepatosplenomegaly
Diagnosis • Mild ascites
• Leukocytois and elevated ESR • Over next few weeks appetite improves and child gets
better
• Liver enzymes are mildly elevated
• Abdominal X ray shows elevated right dome of • Anicetric presentation of hepatitis A can occur
diaphragm Differential diagnosis
• Ultrasound confirms the diagnosis and gives good • Enteric fever
details about the abscess • Falciparum malaria
• CECT is needed in patients with complication • Leptospirosis
• Amebic serology is positive in amebic liver • Viral hemorraghic fever
abscess • Drug induced hepatitis
Differential diagnosis Investigations
• Empyema • Direct hyperbilirubinemia
• Subphrenic abscess • Markedly elevated ALT/AST
• Pneumonia • Normal albumin
• Cholecystits • Milk leukopenia with relative lymphocytosis
Treatment • Ultrasound shows enlarged liver with increased
echogenicity
• Broad spectrum antibiotics for 4–—6 weeks in
pyogenic abscess • Gallbladder wall edema
• Metronidazole is used in amebic abscess for • Viral serologies
10–14 days Management
• Ultrasound guided percutaneous needle aspiration/ • Viral hepatitis is self-limiting which requires no
catheter drainage is warranted in active intervention if there is no complications
j Abscess that fail to improve after 3–4 days of • Maintain hydration with adequate oral intake
treatment • No specific dietary modification is recommended
j Large abscess in left lobe • Monitor the child for appearance of complications
j Impending rupture • Replacement of fat soluble vitamins A, D, E & K
• Surgery is required in frank intraperitoneal rupture or • Reduce stool transit time with syrup Lactulose
multiseptae abscess • GI sterilization with non-absorbable oral antibiotics
Prognosis • Ursodeoxycholic acid (UDCA) 20 mg/kg/day for
cholestasis
• Abscess cavity takes 3–6 months to resolve
completely • No antiviral drugs are required for acute HAV, HBV
and HEV infection
• Cure rate is excellent following antibiotics and
percutaneous drainage • Tenofovir and entecavir can be used in selective cases
of acute HBV infection
Complications
• Acute liver failure
12.19 Acute viral hepatitis • Aplastic anemia
• Pancreatitis
• Virus can affect the liver directly or a part of systemic • Serum sickness, vasculitis like reaction
involvement • Hemolysis causing cola color urine
Etiology • Chronic liver disease
• Hepatitis virus A, B, C, E Prevention
j Hepatitis A virus is most common cause • Safe drinking water
j HAV and HEV transmitted by feco oral route • Proper sanitation
j HCV transmitted by parenteral or vertical • Hand washing
• Cytomegalovirus • Proper food hygiene
• Epstein Barr virus • Screening of blood and blood products
• Herpes simplex virus • Immunization against hepatitis B
192
mebooksfree.com
• > 90% infected neonates becomes carrier compared

12.20 Chronic hepatitis B to 20%–25% children in preschool age
Clinical features
• Defined as persistence of HbsAg for >6 months Three phases have been described
• Age at time of HBV infection determines the
outcome
Anti Anti- HBV

Phase HbsAg Hbs HbeAg Hbe DNA Serum ALT
Immunotolerant Active viral Positive Negative Positive Negative High Normal
replication
Immune Effort of clearing the Positive Negative Positive Negative Reduced Increased
clearance infection by host
Inactive carrier/ Follows after HbeAg Negative Positive Negative Positive Very low Normal
Non replicative seroconversion
phase
Management Biochemical evidence of acute liver injury

j
• Recommendation for treatment are as follows (<8 weeks duration)

j Complete examination and liver function test j No evidence of chronic liver disease
j Serology testing j Hepatic coagulopathy not corrected by parenteral
j Consideration for liver biopsy vitamin K
j Identifying and treating the patients with proper drugs j Prothrombin time > 15 sec or INR >1.5 in the
• Drugs licensed for use in children presence of clinical hepatic encephalopathy
j Interferon j Prothrombin time > 20 sec or INR >2.0 regardless
j Lamivudine of presence of clinical hepatic encephalopathy
j Adefovir • Based on time period between the onset of jaundice
• No treatment required for patients in nonreplicative and development of encephalopathy, it is grouped
phase into 3 subclass
• Children with active disease in immune clearance j Hyperacute liver failure—gap is less than
phase needs treatment 7 days, survival outcome is better with risk of
• Aim of treatment is to achieve reduced levels of HBV development of coma
DNA j Acute liver failure—period of 7–28 days,
Follow up prognosis is poor with risk of cerebral edema
• Needed to monitor disease flares and hepatocelluar j Subacute liver failure—between 4—24 weeks,
carcinoma worst prognosis
• Avoidance of hepatotoxic factors Etiology
• Screening of family members for HbsAg
Neonates and infants Older children
Prevention
• Hepatitis B vaccine is highly recommended • Septicemia • Viral infection
• Dose is 0.5 mL given in 3 doses at 0,1, and 6 months • Inborn errors of j Hepatitis A,B,B + D,E
• Given as intramuscular in deltoid or anterolateral thigh metabolism j Herpes simples
j Tyrosinemia j Adeno virus, EBV

• To prevent perinatal infection Hepatitis B
j Galactosemia • Hepatotoxic drugs
immunoglobulin is given along with hepatitis B
j Hemochromatosis j Valproic acid
vaccine within 12 hrs of birth. Dose of HBIG is 0.5 mL
j Hereditary fructose j INH
intolerance j Halothane
j Mitochondrial j Phenytoin
12.21 Fulminant hepatic failure disorders j Ketaconazole
• Severe birth asphyxia • Hemotological

• Perinatal Herpes malignancy
• Clinical syndrome resulting from massive necrosis of simplex • Hodgkin lymphoma
hepatocytes or from severe impairment in function of • Hemophagocytic • Autoimmune hepatitis
hepatocytes lymphohistiocytosis type 2
• Criteria to diagnose fulminant hepatic failure • Budd Chiari syndrome
193
mebooksfree.com
Pathogenesis neurotransmitters, GABA, and proinflammatory

• Pathogenesis is poorly understood cytokines
• 1-2 % of viral hepatitis progress to liver failure due to Clinical features
massive destruction of hepatocytes • Progressive jaundice
• This occurs due to direct cytotoxic effect of virus or • Fetor hepaticus
immune response to viral antigens • Fever
• Drugs can cause liver injury by producing hepatotoxic • Anorexia
metabolites • Vomiting
• Other factors contribute to progression of liver failure • Abdominal pain
are • Examination shows rapid decrease liver size without
j Impaired hepatocyte regeneration clinical improvement
j Altered parenchymal perfusion • Hepatic encephalopathy
j Endotoxemia j Altered consciousness
j Decreased hepatic reticuloendothelial function j Irritability
• Hepatic encephalopathy is related to increased j Poor feeding
serum levels of nonmetabolized ammonia and false j Rapidly progress to coma
Stages of Hepatic Encephalopathy
Tone and Reponses to

Mental status Behavior Motor activity reflexes pain Pupils
Grade 1 Alert Restless Incoordination Normal Obeys Normal
Oriented Irritable Tremor
Grade 2 Lethargic Combative Yawning Increased Localizes Hyperactive
Confused Euphoric Grimacing tone
Irritated Intention tremor Brisk reflexes
Grade 3 Stupor Sleeps all Decreased motor Up plantar Flexes Hippus
Arousable time activity Clonus
Marked Increased tremor
confusion
Grade 4 Not Unconscious Absent Sustained Extends Dilated
arousable clonus sluggish
Investigations j Anticipation, prevention and treatment of

• Serum bilirubin levels, ALT,AST, and PT to assess liver complication
cell injury • No therapy is known to reverse the hepatocyte injury
• PT ≥ 15 seconds and INR ≥ 1.5 which is not or promote hepatocyte regeneration
corrected by parenteral vitamin K in 6 hours • Patient should be managed in intensive care unit
• Serum electrolytes, renal function test, blood glucose, • Raised ICT is managed with mannitol or
phosphorus, serum ammonia hypertonic saline and with head end elevation to
• Arterial blood gas, coagulation profile and blood culture 30 degrees
• Serum copper, viral serology, autonomic markers and • Hyperventilation to reduce cerebral edema
metabolic screen • Phenytoin may be used for seizures
Treatment • Empirical antibiotics are recommended in sepsis
• Management is based on • Orthotopic liver transplantation is indicated in
j Diagnosing the etiology as it determines prognosis patients where there is acute deterioration of mental
and treatment status, stage 3/4 encephalopathy, PT ≥100 sec/INR ≥
j Assessment of severity of liver failure and timely 6.5, serum bilirubin ≥17.4 mg/dL, worsening lactic
liver transplantation acidosis or the disease is irreversible
194
mebooksfree.com
Specific treatment for acute liver failure in children

Neonatal hemochromatosis Antioxidants, chelation, prenatal IVIG and postnatal exchange transfusion
Tryrosinemia Nitisinone, restriction of phenylalanine and tyrosisne
Galactosemia Galactose and lactose free diet
Hereditary fructose intolerance Fructose free diet
Mitochondrial cytopathies Coenzyme Q10, vitamin E, carnitine
Herpes simplex High dose acyclovir for 21 days
Paracetamol poisoning N—acetyl cysteine
Prognosis
• Mortality is as high as 60%–70% 12.22 Chronic liver disease
• Poor prognostic factors
j Age < 1 year • A spectrum of disorders characterized by ongoing
j Stage 4 encephalopathy liver damage leading to cirrhosis or end stage liver
j INR > 4 disease
j Need for dialysis before transplantation • Duration criteria for diagnosis of chronic liver disease
j Factor V concentration < 25% is 3—6 months
j Lactic acidosis
Etiology
Prolonged cholestasis of infancy Chronic hepatitis
• Biliary atresia • Chronic viral hepatitis, e.g., B, C, and D
• Neonatal hepatitis • Autoimmune hepatitis
• Choledochal cyst • Drug induced hepatitis, e.g., anticancer drugs,
• progressive familial intrahepatic cholestasis (PFIC) anticonvulsants and anti-TB drugs.
• Inspissated bile syndrome
Metabolic or genetic liver diseases Chronic venous congestion or vascular
• Tyrosinemia • Budd–Chiari syndrome
• Glycogen storage disease (GSD type IV and type • Veno–occlusive disease
III—cirrhosis prone) • Noncirrhotic portal fibrosis (NCPF)
• Gaucher’s disease • Congestive heart failure
• Niemann-Pick disease • Constrictive pericarditis
• Wolman disease Copper and iron associated disorders
• Galactosemia • Wilson disease
• Fructosemia • Indian childhood cirrhosis
• Alpha 1-antitrypsin deficiency (rarely)
Miscellaneous
• Mucopolysaccharidosis (Hurler disease)
• Fibropolycystic disease (polycystic disease of liver and
kidney)
• Histiocytosis-X
• Cystic fibrosis
• Fatty liver
• Idiopathic or nutritional cirrhosis.
Clinical features • Abdominal distension

• Presentation depends on etiology and pace of disease • Repeated episodes of jaundice
progression • Failure to thrive
j Chronic insidious type of onset ( common) • Anorexia
j Acute viral hepatitis like onset • Muscle weakness
j Acute on CLD • Ascites
j Asymptomatic presentation • Bleeding manifestations
195
mebooksfree.com
• Characteristic of liver • There is no specific treatment for cirrhosis per se that

Hepatomegaly which is firm to hard, nodular or
j will arrest or reverse the cirrhotic changes
have irregular margins in cirrhosis • Treatment of portal hypertension, ascites and hepatic
j Differential left lobe enlargement encephalopathy
j Non palpable shrunken liver in post necrotic • Treatment of specific cause if any, like Wilson
cirrhosis disease (WD), drug induced hepatitis, and hepatitis
• Cutaneous manifestations B and C
j Spider angiomata, palmar erythema, • Patients with compensated cirrhosis can lead a
clubbing, leukonychia, xanthomata, papular normal life and no specific diet is helpful
acrodermatitis • Hepatic herbal supportives, antioxidants, liver cell
• Testicular and parotid involvement is not seen in membrane protectives, maintenance of adequate
children calories, fluid and electrolytes, vitamin especially fat
• Delayed puberty, gynecomastia and infertility soluble vitamins are routinely recommended with
• Portal hypertension variable outcome
j Splenomegaly, ascites, tortous veins over • Liver transplantation is helpful in EHBA, tyrosinemia,
abdominal wall, esophageal varices GSD, acetyl transferase deficiency and severe bile acid
• Hepatic encephalopathy metabolic defects (PFIC)
j Asterixis, constructional apraxia or altered Complications
sensorium • Hepatic encephalopathy
Diagnosis • Ascites
Common investigations • Hypersplenism
• Liver function test • Variceal bleeding
Low albumin, reversal of albumin–globulin ratio
j • Liver dysfunction like hypoalbuminemia,
and prolonged prothrombin time coagulopathy
j High conjugated bilirubin—liver dysfunction or • Hypoglycemia and growth failure
obstruction • Hepatorenal syndrome
j Raised transaminases—hepatocellular injury • Hepatopulmonary syndrome
j Raised alkaline phosphatase and gamma glutamyl Indicators of poor prognosis
transpeptidaase—biliary disease
• Increasing jaundice • Serum bilirubin
• Ultrasonography—nodular liver, mass, dilated portal • Rapidly decreasing liver >300 mmol/L
vein and collaterals, ascites, splenomegaly size (>17.6 mg/dL)
• Upper GI endoscopy—portal hypertension, varices of • Recurrent or persistent • Decreasing
esophagus and stomach hypoglycemia transaminase levels
• Liver biopsy—beaking of lamina limitans, loss of • Variceal bleed due to • Hypoglycemia <4
architecture in cirrhosis coagulopathy mmol/L needing
Specific to etiology • Clinical acidosis often dextrose
• Hepatic infusions
• Viral markers—HbsAg, HbeAg, anti-Hbe, anti-HBc, encephalopathy grade • Prothrombin time
HBV DNA, HCV RNA 2/3 >60 sec (INR >3.5
• Autoimmune hepatitis—anti—smooth muscle, anti • Age <10 years with and in paracetamol
liver kidney microsomal, antinuclear antibodies jaundice more poisoning >6.5)
• Wilson disease—ceruloplasmin, KF ring than 7 days before • Acid-base pH <7.3
• Alpha -1- antitrypsin deficiency—serum alpha 1 encephalopathy (acetaminophen
antitrypsin levels poison)
• Galactosemia—galatose 1 phosphate uridyl • Raised S. ammonia
transferase assay levels
• Cystic fibrosis—sweat chloride test
• Tryosinemia—urinary succinylacetone level
• Budd chiari syndrome—doppler ultrasonography
• Sclerosing cholangitis—magnetic resonance
cholangio-pancreatography 22.23 Ascites
• Storage disorders—bone marrow, liver biospy
Management • Pathological accumulation of fluid within
• Early detection and management of complications peritoneal cavity
due to decompensated cirrhosis • Can occur at any age and in utero also
196
mebooksfree.com
Causes • Evaluation of ascitic amylase—pancreatitis or

intestinal perforation
Hepatic Gastrointestinal
• Cirrhosis • Infarcted bowel • Uroascites—elevated levels of urea and creatinine in
• Portal hypertension • Perforation ascitic fluid
• Budd-Chiari • Protein-losing • Chylous ascites—high levels of triglycerides giving
syndrome enteropathy milky appearance to ascitic fluid
• Congenital hepatic Neoplasms Treatment
fibrosis • Lymphoma • High-protein and low-fat diet
• Fulminant hepatic • Neuroblastoma • Small ascites do not produce symptoms and requires
failure Pancreatic no treatment
• Lysosomal storage • Pancreatitis • Tense ascites need paracentesis followed by
disease • Ruptured pancreatic treatment of cause for ascites
Renal duct
• Octreotide can be used for chylous ascites
• Nephrotic syndrome Gynecologic
• Obstructive uropathy • Ovarian tumors
• Perforation • Ovarian torsion, 22.24 Spontaneous bacterial
of urinary tract rupture
• Peritoneal dialysis Miscellaneous peritonitis
Cardiac • Systemic lupus
• Heart failure erythematosus • Bacterial infection of ascitic fluid leading on to
• Constrictive pericarditis • Ventriculoperitoneal peritonitis, without an obvious infectious source
Infection shunt
Etiology
• Tuberculosis • Eosinophilic
• Chlamydia ascites • E coli
• Syphilis • Chylous ascites • Klebsiella pneumoniae
• Parvovirus • Hypothyroidism • Pneumococcus
Diagnosis
Clinical features • Positive culture of ascitic fluid
• Abdominal distension • Presence of more than 250 polymorphonuclear
• Early satiety and dysnea cells/mm3
• Increased weight gain • Symptoms and signs consistent with infection
• Physical findings • Without any intraabdominal infection or surgically
j Bulging flanks treatable source of infection
j Dullness on percussion Clinical features
j Shifting dullness, fluid thrill • 10 % of cases can be asymptomatic
j Puddle sign • Abdominal distension—rapid onset
• Dilated abdominal collaterals and caput medusae— • Fever
occur due to liver disease • Malaise
• Elevated JVP seen in cardiac causes • Abdominal pain with tenderness
Investigations Treatment
• Ultrasound is sensitive imaging for ascites • Antibiotics are mainstay of treatment
• Abdominal paracentesis is used to determine the • Third generation cephalosporin for 5 to 7 days is
etiology recommended
• Ascitic fluid should be examined for differential cell • Intravenous albumin 1.5 g/kg at the time of diagnosis
count, albumin level and culture and 1 g/kg on day 3 decreases renal impairment
• Serum to ascitic albumin gradient (SAAG) used to Prevention
diagnose portal hypertension
• High risk patients like cirrhotic patients with low
High gradient ascites Low gradient ascites ascitic fluid total protein levels (< 1 g/dL) and those
(SAAG >1.1 gm/dl ) (SAAG <1.1 gm/dl ) who have recovered from an episode of SBP should
receive long term antibiotics
• Cirrhosis • Peritoneal carcinoma
• Portal vein thrombosis • Tuberculosis Follow-up Paracentesis
• Budd Chiari syndrome • Nephrotic syndrome • Poor clinical response to antibiotics warrants repeat
• Hepatic failure • Pancreatic ascites paracentesis
• Serositis • If PMN count is low and culture negative—give
further course of antibiotics
197
mebooksfree.com
• If PMN count is high and culture shows new Clinical features

organism—change antibiotics • Age group ranges from 4 months—adults
• If PMN count is high and culture shows same • Hemorrhage from esophageal varices precipitated by
organism—suspect secondary bacterial peritonitis minor fever and intercurrent illness
Prognosis • Hepatomegaly
• Splenomegaly with hypersplenism
• Prognosis is poor despite recent advances in • Cirrhosis—Jaundice, ascites, hepatosplenomegaly,
supportive care upper GI bleed
• Budd Chiari syndrome—ascites, hepatomegaly,
tortuous prominent back veins are seen if there is
22.25 Portal hypertension inferior vena cava block
Diagnosis
• Elevation of portal pressure > 10- 12 mm Hg • Ultrasound and doppler study—increased portal
• Normal portal venous pressure is 7 mm Hg vein suggest intra hepatic portal hypertension
Etiology
• Endoscopy—to find varices in esophagus, stomach
and congestive gastropathy
Pre hepatic portal • Portal vein agenesis, atresia, • Selective arteriography of the celiac axis, superior
hypertension stenosis mesenteric artery, and splenic vein may be useful
• Portal vein thrombosis or in precise mapping of the extrahepatic vascular
cavernous transformation anatomy
• Splenic vein thrombosis • Colonoscopy is used to detect lower GI bleed and to
• Increased portal flow show presence of rectal varices
• Arteriovenous fistula • CT or MRI of portovenography useful to find vascular
Intra hepatic • Hepatocellular disease anatomy
portal • Acute and chronic viral • Liver function test are deranged in cirrhotic patients
hypertension hepatitis • Hemogram shows anemia, leukopenia and
• Cirrhosis thrombocytopenia that suggests hypersplenism
• Congenital hepatic fibrosis
• Wilson disease Complications
• α1-Antitrypsin deficiency • Gastrointestinal bleeding from varices
• Glycogen storage disease • Hypersplenism
type IV • Splenic infarcts and splenic rupture
• Extrahepatic biliary atresia • Ascites
• Cystic fibrosis • Hepatic encephalopathy
• Choledochal cyst • Hepato pulmonary syndrome
• Sclerosing cholangitis j Triad of portal hypertension, alteration in arterial
• Intrahepatic bile duct paucity oxygenation and intra pulmonary vascular
Post hepatic • Postsinusoidal obstruction dilatations
portal • Budd-Chiari syndrome • Porto pulmonary syndrome
hypertension • Venoocclusive disease j Pulmonary arterial hypertension associated with
• Constrictive pericarditis severe portal hypertension
Management
• Extra hepatic portal vein obstruction (EHPVO) is • Treatment life threatening hemorrhage
important cause for portal hypertension in children j Fluid resuscitation—crystalloid infusion and RBC
Pathogenesis replacement
• Primary abnormality is increased resistance to portal j Correction of coagulopathy—vitamin K/FFP/
blood flow platelets infusion
• Portosystemic shunting should decompress portal j H2 blockers or proton pump inhibitors—to reduce
system and lower the portal pressure risk of bleeding from gastric erosions
• Despite development of collaterals, portal • To reduce portal pressure with continued bleeding
hypertension is maintained by increase in portal j Vasopressin
venous flow j Nitroglycerin
• Increase in portal flow, likely contributes to an j Somatostatin analog octreotide
increase in variceal transmural pressure • If bleeding continues or after first episode of bleeding
198
mebooksfree.com
j Endoscopic sclerosis or elastic band ligation of Prognosis

esophageal varices • Intrahepatic cause has poor prognosis
• Inspite of pharmacologic and endoscopic treatment, • Progressive liver disease and significant esophageal
if bleeding persists then Sengstaken-Blakemore tube varices ultimately require orthotopic liver
may be placed to stop hemorrhage which compress transplantation
esophageal and gastric varices mechanically
• Transjugular intrahepatic portosystemic shunt
(TIPSS)—stent between right hepatic vein and right
or left branch of portal vein Please visit MedEnact to access chapter wise MCQs and
• Porto-systemic shunt surgery previous year pediatrics theory questions asked in various
• Orthotopic liver transplantation final MBBS University examinations.
199
mebooksfree.com
Chapter | 13 |
Cardiovascular system
• As a result of increase in SVR and decrease in

13.1 Fetal circulation PVR, there is reversal of shunt in ductus arteriosus
from aorta to pulmonary artery, which was from
pulmonary artery to aorta in fetal circulation.
• In fetal circulation, the left and right ventricles are in
a parallel circuit, whereas in children and adults, it
is in series. The ductus venosus, foramen ovale, and
ductus arteriosus are important structures needed
for maintaining this parallel circulation. Placenta
provides gas and metabolites for exchange while
the lungs do not participate in gas exchange and
pulmonary circulation are constricted.
Fetal circulatory flow:
• Oxygenated blood from placenta enters fetus via the
umbilical vein (UV). Approximately half of UV blood
enters the liver while the remaining half is shunted
and joins the IVC via the ductus venosus.
• The blood from lower limbs and umbilical vein enters
right atrium and are preferentially redirected across
the foramen ovale into the left atrium. The blood
then reaches LV and is pumped into the aorta.
• Blood entering right atrium via SVC mostly crosses
tricuspid valve and flows into right ventricle. From
RV, blood is ejected into pulmonary artery. Only
10% of RV outflow enters lungs due to pulmonary
vasoconstriction. The remaining 90% blood bypasses
lungs and enters into descending aorta via ductus
arteriosus. This blood perfuses the lower half of the
body. The venous blood from lower limbs returns to
placenta via the paired umbilical arteries (Fig. 13.1).
Circulatory adjustments at birth
• Removal of placenta
j Increase in systemic vascular resistance (SVR) and
closure of ductus venosus
• Lung expansion results in
j Decrease in pulmonary vascular resistance (PVR)
j Functional closure of foramen ovale Figure 13.1 Fetal circulation.
j Closure of ductus arteriosus Source: Nelson textbook of Pediatrics, 2011
200
mebooksfree.com
Cardiovascular system Chapter | 13 |
Perinatal changes influencing left to right shunt

Before birth: 13.2 Acyanotic congenital heart
• Gas exchange in the fetus is primarily a placental disease (ACCHD)
function
• Minimal pulmonary blood flow (PBF), higher
pulmonary vascular resistance (PVR) and low
• The left- to-right shunt implies pumping of
oxygenated blood back to the pulmonary circulation,
systemic vascular resistance SVR (resistance in
e.g.,:
placental circuit is low) are characteristic
j Atrial Septal Defects (ASD)
After birth: j Ventricular Septal Defects (VSD)
• Increase in arterial PaO2 decreases the PVR through j Patent Ductus Arteriosus (PDA)
arteriolar dilation but pulmonary artery pressure • The clinical manifestations are secondary to increased
(PAP) remains elevated. Pulmonary smooth muscle blood flow through pulmonary circulation and
involution and a postnatal rise in surface area of ‘systemic steal’ phenomenon (shunting of systemic
pulmonary vascular bed allows progressive decrease blood flow into pulmonary circulation).
in PVR over the first 8–12 weeks. Termination of Classification
placental low resistant circuit increases systemic Left-to-right shunts—Pretricuspid (e.g., ASD) and post-
vascular resistance (SVR) thereby promoting left–to– tricuspid shunts (e.g., VSD, PDA) Fig. 13.2.
right shunting. Pre -tricuspid shunts:
• Timing of changes in pulmonary and systemic • They occur at the level of the atria and the volume of
vascular resistance is extremely crucial in dictating the shunt is decided by relative stiffness (compliance) of
onset of clinical symptoms. Significant left-to-right the two ventricles. Since the right ventricle (RV) is
shunts start after 8–12 weeks. Size of defect is the hypertrophied and relatively stiff (noncompliant)
primary factor deciding the magnitude of shunting. at birth and during early infancy, pretricuspid shunts
Larger defects allow larger shunts leading on to early tend to be small and may not manifest clinically. Over
onset heart failure. the years the right ventricle progressively enlarges and
Figure 13.2 Normal blood flow through the heart and lungs after birth.
201
mebooksfree.com
the pulmonary vasculature becomes more capacious Hemodynamics:

to accommodate the excessive pulmonary blood flow. • Factors affecting the magnitude of left-to-right shunting
• Common physical examination findings are j Size of the defect
associated are: j Compliance of the right and left ventricles
j Ejection Systolic Murmur (ESM) in pulmonary (compliance of RV is greater than LV)
area as the RV deals with a larger volume of blood j Vascular resistance in the pulmonary and systemic
flow which is ejected into the pulmonary artery circuits
j Diastolic flow murmur due to excessive flow across • In Early Life, RV muscular wall is thick and less
the relatively larger tricuspid valve compliant, thereby limiting the left-to-right shunt. As
j Widely fixed second heart sound (S2) because of the infant grows, pulmonary vascular resistance falls,
the prolonged right ventricular ejection time. RV wall becomes progressively thinner (compliance
j Irreversible changes in the pulmonary vasculature increases) and the left-to-right shunt across the defect
producing pulmonary arterial hypertension (PAH) increases.
j Features of Right heart enlargement (Right atrium • The extra volume of blood that flows from LA to RA
and ventricle ) through the defect reaches the RV and then pumped
Post-tricuspid shunts: into lungs through pulmonary artery. Though LA
• They occur at the level of ventricles (e.g., Ventricular receives increased pulmonary vascular return from the
Septal Defects (VSD), or great vessels (e.g., Patent lungs, it never enlarges as the LA does not retain this
Ductus Arteriosus (PDA) and Aorto Pulmonary blood but immediately they shunt it across to RA. LV
window). The shunted blood passes through the and Aorta are of normal in size (Fig. 13.3A).
pulmonary vasculature returns via the left atrium (LA) Clinical presentation
to result in diastolic volume overload of the left ventricle • Most of the cases are asymptomatic since PA can
(LV). The hemodynamic and clinical features are handle large blood flow without producing CCF.
determined by the size of the defect. Symptoms begin Some cases can have palpitation, fatigue, exertional
in the early infancy, following regression of elevated dyspnea and recurrent respiratory tract infection due
pulmonary vascular resistance in the newborn period. to increased pulmonary blood flow. Other features of
• Common physical examination findings associated syndromes like Down’s syndrome, Holt–
associated are Oram syndrome, TAR syndrome, Edward’s syndrome,
j Murmur from the defect, due to transmission Ellis van creveld syndrome, Fetal alcohol syndrome
of pressure from the systemic to the pulmonary and Fetal hydantoin syndrome may be present.
circulation during systole (at ventricular level)
or during both systole and diastole (at great
arteries level).
j Apical mid-diastolic murmur due to excessive
blood flow through the mitral valve.
j Elevation in pulmonary artery pressures in large
(or unrestrictive) post-tricuspid shunts.
13.3 Atrial septal defects (ASD)
• Occurs as an isolated anomaly (10% of CHD) or

associated anomaly (in 50% of CHD) and are more
common in females.
• ASDs can occur anywhere on the atrial septum
depending on the defective embryonic septal structure
• Types of ASD
j Ostium secundum (OS): Most common form of
ASD (70% of ASD). Defect in the region of the
fossa ovalis
j Ostium primum (OP): Second most common
type (15% of ASD). Associated with endocardial
cushion defect.
j Others: Sinus venosus type (10% of ASD) and Figure 13.3 (A) Hemodynamics of ASD (Bold lines implies
coronary sinus type. enlargement, Bold arrow implies the increased blood flow).
202
mebooksfree.com
Figure 13.3 (B) Auscultatory findings of ASD.
• On examination, Pulse and JVP are usually normal • CXR—Jug handle appearance (Enlarged RA and RV),
unless associated pulmonary hypertension (PHT) prominent pulmonary artery segment and increased
is present where JVP may show large ‘a’ waves. pulmonary vascular markings
Cardiovascular examination shows mild left • Echocardiography
precordial bulge, normal apical impulse, parasternal j Size and type of defect—subcostal four chamber
pulsation, Parasternal heave and systolic thrill in 2nd view.
intercostal space. Pulmonic ejection clicks can be j RA/RV enlargement
heard. Heart sound S1 is normal. Management
• Classical auscultation finding of ASD are
j Wide splitting of 2nd heart sound (delayed RV • Approximately 40% of ostium secundum defects
close spontaneously by 4 years of age. Almost 100%
contraction and delayed closure of pulmonary
of defects <3 mm closes spontaneously within 1 year
valve due to RBBB)
6 month of age, while 80% of 3 to 8 mm defect closes
j Fixed splitting of 2nd heart sound (abolished
spontaneously by 1 year 6 month of age. Spontaneous
respiratory related variation in systemic venous
closure of residual defects of >8 mm in >4 years is
return) in all phases of respiration which becomes
rare.
narrow with the onset of PHT
j Nonsurgical closure—Is the preferred method
j Ejection systolic murmur in pulmonary area.
using catheter delivered closure device like
Murmur in ASD is not due to the shunt (low
amplatzer septal occluder, Helexaeptal occlude for
pressure gradient unlike VSD), but due to increase
secundum ASD.
blood in the pulmonary valve (Fig. 13.3B).
Surgical closure with pericardial or Teflon
• Tricuspid area may have delayed diastolic murmur
j
patch is done in ostium secondum ASD with

and early diastolic murmur due to increased blood
pulmonary to systemic blood flow ratio of more
flow across the tricuspid valve which produces relative
than 1.5:1.
stenosis (in large ASD).
Complication:
Diagnosis
• ECG • Though infective endocarditis does not occur in
j Ostium Secundum—Prolonged PR, RAD, RVH, isolated ASD, risk of paradoxical embolization
RBBB with rsR’ pattern in V1 (dilated RV prolongs and atrial arrhythmias are present in adults. Other
the depolarization time) complications include PHT and Eisenmenger
j Ostium Primum—LAD syndrome.
203
mebooksfree.com
PA and LA. The RV remains normal in size, till the

13.4 Ventricular septal defect (VSD) onset of pulmonary hypertension. Signs of CCF do
not appear before 6–8 weeks as the PVR remains high.
Definition: Hemodynamics of the VSD and PDA remains the same
• VSD is the most common congenital heart disease producing LV dysfunction (Fig. 13.4A).
(∼20% cases). The ventricular septum is divided into
small membranous and large muscular part.
• The membranous septum defect often involves the
adjacent muscular septum
j Perimembranous VSD—most common VSD—
(70% VSD cases)
• The muscular septum is further divided into
j Inlet
j Trabecular/muscular (20% of all VSD)—when its
multiple defects then its named as Swiss Cheese
type. Subdivided into Anterior, Posterior, Mid, and
Apical types
j Outlet—Supracristal, conal and sub pulmonary
types; Associated with aortic insufficiency
Hemodynamics:
• The magnitude of the left to right shunt in VSD
depends on
j Size of the defect when its size is small
j Level of PVR when the defect size is large, but not
by the location of the defect.
• In VSD the left to right shunt at ventricular level occurs
during the systole, the amount of blood from the LV
enters the PA through RV, with no volume over load in
RV. This extra volume of shunted blood from PA enters
the lung, delivered back to left atrium and left ventricle. Figure 13.4 (A) Hemodynamics of VSD (Bold lines implies
Thus LV volume over load occurs in VSD, with dilated enlargement, Bold arrow implies the increased blood flow).
Figure 13.4 (B) Auscultatory findings of VSD.
204
mebooksfree.com
Table 13.1 Presentation of different sized VSD
Large VSD Low Large with increased

Small VSD Moderate VSD PVR PVR
Hemodynamics • Left to right shunt • Left to right shunt • Greater amount • Reduction in left to
is less is more, thus PA, of shunt than right shunt.
• No PA, LA, LV LA and LV dilate. moderate VSD
dilatation • Significant volume producing RV
• Minimal volume over load on LV dysfunction.
overload on LV
Clinical Features • Asymptomatic • Delayed growth, • Features of CCF • Cyanosis
(Fig. 13.4B) • Regurgitant recurrent chest • Precordial bulge, • Murmur intensity
systolic murmur infection hyper dynamic decrease, S2 is single
• P2 normal • Holosystolic chest and loud (PAH)
murmur • Same as Moderate
• Increased flow VSD
of blood across
MV produces mid
diastolic rumble at
the apex
• P2 may increase
Chest • No cardiomegaly • Cardiomegaly (LV • Bi ventricular • Cardiomegaly
radiograph enlarged) enlargement, decreases as volume
• Pulmonary overload on LV
congestion decreases
• Prominent pulmonary
arteries
ECG • No LVH • LVH—volume • Biventricular • LVH, LAH disappears
overload type but hypertrophy, LAH while the RVH
no RVH increases.
• Spontaneous closure of VSD—60% of small / • Surgical closure is done by 1 year of age for children
moderate muscular VSD closes spontaneously upto with pulmonary artery pressure more than 50% of
8 years and 35% small membranous VSD closes systemic pressure or done after 1 year of age if Qp/Qs
spontaneously. ratio is more than 2:1.
• Surgery is contraindicated in children with
Clinical Presentation: Table 13.1
pulmonary vascular obstructive disease or with right
Investigation
to left shunt.
• ECG • RBBB, left anterior hemi block and the residual VSD
• CXR are the usual complications of surgery.
• 2D Echocardiography—To identify the location,
size, and number of the defect/magnitude of the
shunt/PA pressure/identification of other associated
defects 13.5 Patent ductus arteriosus (PDA)
Treatment:
Medical: • PDA occurs in 10% of all CHD and is more common
in preterm (80% in preterm less than 1200 g) than in
• Treatment of CCF with diuretics (furosemide/
potassium sparing diuretics) along with ACE terms
inhibitors and treatment for anemia, failure to thrive • More common in females than in males.
should be done till spontaneous closure occurs. Pathology:
Surgical: • Persistent patency of ductus arteriosus (normal fetal
• In large VSD, surgical closure is done within the first structure)—A cone shaped structure arises 10 mm
6 months of life, if growth failure occurs in spite of distal to the origin of the left subclavian artery, and
medical management. connects pulmonary trunk and descending aorta.
205
mebooksfree.com
Hemodynamics:
• Degree of left to right shunt depends on the resistance
in the ductus (if the ductus is small) and pulmonary
vasculature (if the ductus is large).
• In small PDA, LV enlargement is minimal. In large
PDA, the LA, and LV are enlarged. Due to pulmonary
hypertension, there is RV enlargement as well leading
on to bi-ventricular hypertrophy. If untreated, can
result in pulmonary vascular obstructive disease
producing bi-directional shunt at the ductus (decrease
in the continuous murmur) and thus heart size may
become normal in the chest radiograph but the main
pulmonary segment is dilated (Fig. 13.5A).
Clinical Presentation:
• When ductus is small, patients are usually
asymptomatic. Large PDA with significant shunt
invariably presents with CCF.
• On examination, characteristic finding of bounding
peripheral pulses and wide pulse pressure were seen.
• Physical findings associated with large PDA
j Hyperactive precordium, systolic thrill at upper
left sternal border, loud P2 (if pulmonary
hypertension). Figure 13.5 (A) Hemodynamics of PDA (Bold lines implies
j Classical harsh, continuous, machinery murmur enlargement, Bold arrow implies the increased blood flow).
in upper left sternal border (there is a significant
pressure gradient between aorta and pulmonary
trunk throughout the cardiac cycle)
j Apical diastolic rumble (relative stenosis of the
mitral valve) (Fig. 13.5B)
• If pulmonary vascular obstructive disease sets in,
there is reversal of shunt (right to left shunt through
ductus) and hence differential cyanosis manifests
Figure 13.5 (B) The auscultatory findings of PDA.
206
mebooksfree.com
(only in the lower part of the body) and the murmur • Ductus dependent lesions present in the first week
will not be continuous anymore. of life when ductus closes. PGE1 infusion should be
Investigation: initiated empirically in suspected cases.
• Chest radiograph: May be normal in small PDA; • Management options include medical therapy,
Cardiomegaly and increased pulmonary vascular temporary or permanent surgical correction
markings in large PDA • The cyanosis is more in cyanotic CHDs that have
• ECG low pulmonary blood flow. The cyanosis is less—in
j LVH cyanotic CHDs that have pulmonary over circulation.
j RVH if pulmonary vascular obstructive disease (e.g., TOF appears cyanotic while Transposition of
develops Great Arteries may not appear cyanotic).
j Biventricular hypertrophy in large PDAs • Oxygen which is a potent pulmonary vasodilator
• ECHO—to assess the size in supra sternal view, when administered to the infant with a cyanotic
dimensions of the LA and LV gives and indirect CHD who has pulmonary over circulation physiology
assessment of the left to right shunt. (Total Anomalous Pulmonary Venous Return, truncus
arteriosus, single ventricle states without pulmonary
Treatment:
stenosis) may worsen the situation. Similarly,
• Asymptomatic small PDA doesn’t need treatment
sildenafil is also contraindicated.
and they should be followed for 6 months for
spontaneous closure.
Medical management:
• Pharmacological closure with indomethacin/
ibuprofen is attempted in preterm with symptomatic 13.7 Tetralogy of fallot (TOF)
PDA, unless contraindicated by renal failure or
bleeding tendency in the infant.
Surgical closure: • The four components of tetralogy of Fallot
(TOF) are
• Surgical ligation is done if medical management j Ventricular Septal Defect
fails. Commonly used approach is by postero-
j Aortic override of the ventricular septum
lateral thoracotomy—PDA either ligated/
j Right ventricular outflow tract obstruction
hemoclipped.
(RVOT)/Pulmonary stenosis (PS)
Nonsurgical closure:
Right ventricular hypertrophy (RVH)
• This procedure is indicated in symptomatic PDA with
j
CCF and is contraindicated once the Eisenmenger’s • Embryologically the series of events which occurs
in TOF
syndrome or pulmonary vascular obstructive disease
sets in. • Associated features: Anomalous origin of the left
anterior descending coronary artery (LAD) from the
• Gianturco stainless steel coils/Amplatzer duct right coronary artery, a right aortic arch and ASD.
occluder are used for closure. Injury to recurrent
laryngeal nerve, phrenic nerve or thoracic duct is a Hemodynamics:
known complication of this procedure. • The two important abnormalities required for
TOF are
j Large VSD and
j RVOT in the form of pulmonary infundibular/
13.6 Cyanotic congenital heart valvular stenosis.
disease (CCHD) • RVH is the result of RVOT and overriding of aorta
may not be present always.
• Most CCHDs have major structural cardiac defects • Hypoxemia and cyanosis depends on amount of
that are often diagnosed by fetal echocardiography at pulmonary blood flow that is in turn controlled by
18–22 weeks. the degree of right ventricular outflow obstruction.
207
mebooksfree.com
Either the increase in pulmonary vascular resistance • Pan digital clubbing is an important finding in
or decrease in systemic vascular resistance will TOF—one hypothesis suggests that “fragmentation
increase the right to left shunt and hence the cyanosis. of megakaryocytes (from which the platelets derive)
j Severe obstruction—Systemic venous blood occurs in the pulmonary circulation which leads to
entering the RV will exit more easily through release of Platelet Derived Growth Factor (PDGF)
the VSD into the LV (right to left shunt), thereby and Transforming Growth Factor β (TGF β). This
causing systemic desaturation and cyanosis. This phenomenon is restricted to pulmonary circulation
is associated with a ductus dependent pulmonary in a normal person. In TOF, there is a right to left
circulation. shunt which spills these megakaryocytes into systemic
j Mild obstruction (PINK TOF)—Flow across circulation where they get trapped in the capillaries
the VSD (left-to-right) and pulmonary valve are in the digits and release growth factors and produce
normal. clubbing
• Mere presence of VSD and PS is not TOF. VSD in Cyanotic spell (hypoxic, blue, or tet spells)
TOF should be as large as an aortic valve annulus to
• It is a unique clinical feature of tetralogy of fallot
equalize the pressure between RV and LV.
• Occurs in less than 2 years of age.
Clinical presentation • Events like waking up in the morning or exertion
• Mild (RVOT) obstruction—Often presents with an (excessive crying/straining for defecation) which
isolated murmur (Pink tetralogy). Behaves similar to decreases the systemic vascular resistance, initiates
an isolated moderate VSD, since the regurgitant VSD the spell.
murmur masks the ejection murmur of PS. • Squatting—toddlers assume this position after
• Severe obstruction (PS) presents with cyanosis, a physical exertion when they are dusky and tachypneic
prominent left lower parasternal heave, S2—loud and to relieve these symptoms (Fig. 13.6B).
single (due to anterior position of the aorta and soft • Child Starts crying → becomes more hyperpneic and
closure of the pulmonary valve respectively). restless → deepening of cyanosis (disappearance of
• Harsh ejection systolic murmur best heard in the left heart murmur) → Gasping respiration → syncope
mid-parasternal area (due to sub-RV outflow tract may follow → severe spells can lead to convulsions
obstruction and not due to VSD which is large and or hemiparesis. This vicious cycle continues if not
unrestrictive in TOF). Intensity of the murmur is intervened.
inversely proportional to the degree of obstruction Mechanism of cyanotic spell:
(Fig. 13.6A). This disappears during hyper cyanotic • Though the pulmonary spasm (infundibular spasm)
spell (since most blood in the RV shunts through the is believed to trigger this spell, it is the fall in systemic
VSD instead of going through the RV outflow tract). vascular resistance which has the major role in
Figure 13.6 (A) The auscultatory finding of TOF.
208
mebooksfree.com
j To decrease the systemic venous return

j To increase the systemic vascular resistance
j Oral propranolol therapy—0.5 to 1.5 mg/kg every
6 hourly
j Iron replacement
Surgical correction:
• Patch closure of the VSD and RV muscle bundle
resection with or without a trans pulmonary valve
annulus patch or pulmonary valvotomy at 6–12
Figure 13.6 (B) Squatting equivalents in TOF. months of life.
j Blalock–Taussig shunt—As a palliative
controlling the degree of right to left shunt and hence procedure when the branch pulmonary
the cyanosis. arteries are hypoplastic regardless of the
• Paroxysmal atrial tachycardia or hypovolemia associated anomalies followed by complete
intracardiac repair. The common complications
Investigation:
are pulmonary insufficiency, ventricular
• ECG: Right ventricular hypertrophy and right axis arrhythmias, and severe QRS duration
deviation.
prolongation on ECG
• Chest X ray shows boot shaped heart; lung fields
may be oligemic or normal (due to PS or right to left Complication of TOF:
shunt) or with right sided aortic arch. • Hypoxic spells and Squatting.
• ECHO confirms the diagnosis, coronary angiogram • Cerebral abscesses from septic emboli, cerebral
delineates the origin of the left anterior descending thrombosis/stroke due to dehydration and bacterial
coronary. endocarditis may occur.
• Polycythemia as a result of increased erythropoietin
Treatment
stimulation due to low arterial oxygen saturation.
Medical treatment
Though they have polycythemia, smear shows
• Cyanotic spell (Table 13.2): Aim: all measures to microcytic RBCs due to relative iron deficiency.
decrease the right to left shunt, like • Bleeding disorder, gout.
Table 13.2 Management of Cyanotic spells
Treatment Effect Mechanism of action

Knee chest position • Kinks the vein of the • Decreases the systemic venous return to the right heart and
lower limb at the hip. thus decrease the amount of right to left shunt.
• Kinks the arteries of the • Reduces the arterial blood flow to legs
lower limb at the hip. • Reduces venous return from lower limbs.
• Calms the baby • Increases the systemic vascular resistance and hence the
right to left shunt.
• Decreases the anxiety/adrenergic surge
Administration of oxygen Increases the arterial oxy- Decreases the hyperpnea
gen saturation
Morphine sulphate Suppresses the respiratory Decreases the hyperpnea
(0.2 mg/kg)S.C. center
Ketamine Increase the systemic vascular resistance and sedates the child
Propranolol use in acute • Slows the heart rate and relieves the infundibular spasm
situation • Decreases the vasodilating effect of beta adrenergic stimulants
• In chronic use, propranolol stabilizes the vascular reactiv-
ity and thus paroxysmal fall in systemic vascular resistance
which initiates the spell.
Vasoconstrictors like phe- Increase the systemic vascular resistance.
nylephrine
Soda bicarbonate correction To correct acidosis This reduces respiratory centre stimulation by acidosis
1 meq/kg administered iv
209
mebooksfree.com
• Severity of the cyanosis is dependent upon the

13.8 Transposition of the great amount of mixing of blood between the systemic and
arteries (TGA) pulmonary circulations. Reverse differential cyanosis
is hallmark of TGA with intact ventricular septum: the
pulse oximeter will show a significantly lower saturation
• The aorta and pulmonary arteries arise from the
wrong ventricles resulting in deoxygenated blood in the right hand (preductal) than in the foot.
from the right ventricle being delivered to the • TGA with VSD presents with mild cyanosis,
body and oxygenated blood from the left ventricle congestive heart failure from pulmonary
circulating back to the lungs. overcirculation and failure to thrive because of the
VSD in early infancy.
• D-TGA is a classic complete TGA with the aorta
located anteriorly and to the right (dextro–D) of Investigation:
pulmonary artery. In L-TGA the aorta is located to the • Newborn ECG will be normal or RVH or BVH can be
left of the pulmonary artery. evident.
Hemodynamics: • Chest radiograph shows egg shaped heart with a
narrow base (as the great arteries lie on top of each
• Majority of TGA have intact ventricular septum, while
25% have VSD (Perimembranous or muscular). other) and increased pulmonary vascular markings.
• To survive, there has to be mixing of blood between • Echocardiogram confirms the diagnosis.
the systemic and pulmonary circulations either at the Treatment:
atrial level (preferably) or via patent ductus arteriosus Medical treatment:
or through a VSD. The right ventricle fails to undergo • PGE1 infusion—maintains patency of Ductus
the normal involution of hypertrophy after birth as it arteriosus
pumps to the high pressure systemic circulation. The Surgical Treatment:
left ventricle will undergo this involution rapidly in
• If peripheral saturation <60%, balloon atrial
the absence of a large high pressure shunt such as a
septostomy (e.g., Rash-kind procedure) should be
VSD or PDA.
performed to improve atrial level mixing.
Clinical Presentation • The corrective surgery for TGV is the arterial switch
• Transposition with intact ventricular septum operation, where the aorta and pulmonary arteries are
usually present in first 24 h of life with severe transected above their roots and reanastomosed to the
cyanosis, tachypnea without retractions. There anatomically correct roots.
may be no murmur on auscultation and the only • They are done preferably in early neonatal period
clue can be a single loud second heart sound (<2 weeks of age) to avoid the “deconditioning”
(Fig. 13.7). of the left ventricle. If left ventricle has already
Figure 13.7 Auscultatory findings of TGA.

210
mebooksfree.com
deconditioned, the atrial switch operation (Mustard Cyanosis will be more profound if pulmonary
or Senning) may be performed but they are prone to blood flow is restricted. On the other hand, if there
developing atrial arrhythmias. TGA with large VSD— is excessive pulmonary blood flow, the peripheral
operation can be delayed saturations will be on the higher side and cyanosis
• The neonatal arterial switch operation is associated may be missed.
with excellent outcome. • Infants present with tachypnea, poor feeding skills
and will have signs of congestive heart failure and
pulmonary over circulation.
13.9 Tricuspid atresia • The cardiovascular examination shows a prominent
apical impulse (LV volume overload). A loud harsh
pan systolic murmur (PSM) due to flow across
• Obstruction in the normal flow from the right atrium the VSD may be heard. In case of pulmonary over
to the right ventricle, due to absence of tricuspid circulation, increased flow across the mitral valve
valve. produces a mid-diastolic rumble (Fig. 13.8).
Hemodynamics: • Patients will have progressive cyanosis as the VSD
• The tricuspid valve is replaced by a tissue becomes smaller over time with most types of
• An ASD or VSD is necessary for an obligatory right-to- tricuspid atresia. Patients with tricuspid atresia with
left shunt. or without transposition and a large VSD can develop
• Systemic venous blood entering the right atrium finds congestive heart failure and subsequent pulmonary
an outlet through the ASD/PFO. There is complete hypertension resulting in death in infancy or the
mixing of pulmonary and systemic venous blood in late development of pulmonary vascular obstructive
the left atrium. disease.
• In case of normally related great arteries, pulmonary Investigation:
blood flow is supplied through the VSD. The amount • The ECG of a patient with tricuspid atresia and
of pulmonary flow will thus be dependent on the size normally related great arteries is unusual with a
of the VSD. leftward and superior QRS axis (270–360°) with
• With transposed great arteries, the aorta arises from LVH. In the presence of transposed great arteries, the
the right ventricle and systemic flow to the aorta is mean QRS axis remains leftward but may be inferior
dependent on the size of the VSD. (0–90°) in half of the cases. The P wave may be tall.
Presentation • An echocardiogram is diagnostic and provides
• The neonate with tricuspid atresia will have cyanosis complete information required to execute a treatment
that might be picked up in the first week of life. plan.
Figure 13.8 The auscultatory findings of Tricuspid atresia with VSD/PDA.
211
mebooksfree.com
Treatment: j They have associated complex heart defects (like

• Only palliative surgery is possible for all types of heterotaxy syndromes especially polysplenia ) and
tricuspid atresias. The Fontan palliation is carried out a PFO or an ASD is necessary for sustaining life.
in 3 steps. Clinical presentation
• A patient who has undergone complete Fontan • The Obstructed TAPVR will present at birth with
palliation has a 10-year survival of close to 80%. respiratory distress and cyanosis. Other types with
unrestricted flow can present in neonatal period or
in infancy with symptoms of congestive heart failure
13.10 Total anomalous pulmonary repeated respiratory infections and failure to thrive.
Cyanosis may be slight with systemic saturation in
venous return (TAPVR) the high 80’s or low 90’s but are never completely
normal.
• The pulmonary veins drain into the systemic veins or • Prominent left parasternal heave/precordial
right atrium instead of left atrium. bulge (RV volume overload). S2 widely split
Hemodynamics: with accentuated P2, flow murmur across the
• The persistence of branch pulmonary vein pulmonary (ESM) and mitral valves (mid diastolic
connections with the systemic veins (like cardinal, rumble) are the significant cardiac findings
umbilical and vitelline) that should disappear during (quintuple rhythm). In Supra-cardiactype a
normal embryologic development. The connections continuous murmur in the infraclavicular area may
may have obstructions (intrinsic or extrinsic) at be heard (Fig. 13.9A).
various points. Investigation:
• Common types include • The chest radiograph shows ‘Snowman’ sign or
j Supracardiac (pulmonary venous drains into ‘cottage loaf,’ or ‘Fig. of 8’ appearance (Fig. 13.9B) in
innominate vein or superior vena cava) is the most supracardiac TAPVR.
common type • In Obstructed TAPVR the radiograph resembles
j Infracardiac/obstructive (pulmonary venous that seen in meconium aspiration syndrome/
drains into portal vein, inferior vena cava) have persistent pulmonary hypertension with often dense
early presentation opacification of both lung fields. Pulmonary venous
j Cardiac (pulmonary venous drains into right edema (bat wing) may be prominent.
atrium directly or coronary sinus) or • ECG—shows RVH (volume overload) and right axis
j Mixed type with more than one anomalous site. deviation.
Figure 13.9 (A) The auscultatory findings of TAPVR.
212
mebooksfree.com
• On auscultation there is
j Loud S1
j Accentuated P2
j Opening Snap (rheumatic MS)
j Low frequency Mid diastolic rumble at apex and
crescendo presystolic murmur at apex
j High frequency diastolic rumble of pulmonary
regurgitation at the upper left sternal border
(Fig. 13.10).
Investigation:
Figure 13.9 (B) The SNOWMAN appearance in the chest • The ECG shows RAD, LAH, RVH.
radiograph of Supra cardiac TAPVR. • Chest X-ray shows LA/RV enlargement, Kerley’s B
lines, increased pulmonary vascularity in the upper
lobes.
• The echocardiogram defines the anatomy sufficiently. • The ECHO is to examine the structures like the valve,
Pulmonary hypertension will be severe in obstructed supra valvular region, chordae, and papillary muscle.
TAPVR. j The slow diastolic closure of anterior mitral leaflet,
Treatment: anterior movement of posterior leaflet during
• In Obstructed TAPVR the use of prostaglandin diastole, multiple echoes of thick mitral leaflet in
infusion, nitric oxide, sildenafil are contraindicated. ECHO suggests MS of rheumatic origin.
Obstructed TAPVR is a surgical emergency with high • Doppler study is used to estimate pressure gradient.
perioperative mortality. j <4–5 mm Hg—Mild stenosis
j 6–12 mm H g—Moderate stenosis
j More than 13 mm Hg—Severe stenosis
13.11 Valvular lesions Treatment:

Medical:
• Mild to moderate cases need anti failure measures
13.11.1 Mitral stenosis (digoxin/diuretic).
• Rheumatic origin of mitral stenosis is rare in • Balloon valve dilatation in children with failure to
children as it needs 5–10 years from initial attack to thrive and recurrent respiratory infection.
develop. • Atrial fibrillation warrants Digoxin, Intravenous
Procainamide, and warfarin if chronic Atrial
• Isolated congenital MS is rare (usually associated with
Shone complex). Fibrillation is present.
• Congenital MS have more than one level of • Dental hygiene/prevention of recurrence.
obstruction, like fusion of leaflets/single papillary Surgical:
muscle with parachute mitral valve/supra valvular • The closed or open mitral commissurotomy is done
mitral ring obstruction/with hypo plastic left heart for MS without calcification
syndrome. • Mitral valve replacement—Prosthetic (Starr—
• Features of Rheumatic MS are thickening of leaflets Edwards, St. Jude) or bio prosthesis with warfarin/
and fusion of commissures low dose aspirin is done for patients with
Clinical features: j Severely damaged/calcified valve
• Mild cases are usually asymptomatic. j Severe MS/failed Balloon dilation
• Severe MS can present with breathlessness and failure j Recurrent Atrial Fibrillation/thromboembolic
to thrive. phenomenon/hemoptysis
• On physical examination there are precordial j The Postoperative CCF is the most common
pulsations and dilated neck veins. complication.
Hemodynamics:
213
mebooksfree.com
Figure 13.10 The auscultatory findings of Mitral Stenosis (MS).
Complications: j Any lesion that dilates LV and thus the mitral valve
• Failure to thrive. annulus can produce MR (like aortic regurgitation
• Recurrence of rheumatic fever worsens the stenosis. and dilated cardiomyopathy).
• Infective endocarditis, atrial fibrillation and Clinical features:
thromboembolism are rare in children.
• Appearance of hemoptysis indicates long standing • Mild MR is usually asymptomatic. The cardio vascular
findings are
pulmonary venous hypertension.
j Heaving, hyper dynamic apical impulse in severe
MR.
13.11.2 Mitral regurgitation (MR) j S1 is soft/diminished, S2 split wide (early closure
of aortic valve) and S3 may be heard.
• Mitral regurgitation is the most common valvular j Hallmark of MR—Regurgitant systolic murmur
involvement in children with Rheumatic Heart Disease.
of grade 2 to 4/6, at the apex, starting with S1
• Congenital MR is associated with AV canal and transmits to left axilla, best heard in the left
defect while acquired MR is mostly of rheumatic
decubitus.
origin.
j Low frequency diastolic rumble at the apex may be
Etiology heard (Fig. 13.11).
• Congenital MR is due to cleft in the mitral valve or Investigation:
associated with AV canal defect
• The ECG shows LVH, with or without LAH, rarely AF.
• Acquired: • The Chest X-ray shows LV/LA enlarged and
Rheumatic MR is due to fibrosis of mitral valve
pulmonary venous congestion if CCF develops.
j
leaflet.
Hemodynamics:
214
mebooksfree.com
Figure 13.11 The auscultatory findings in Mitral regurgitation (MR).
• The ECHO shows dilated LA/LV, and degree of Complications:

dilation related to severity (severity assessed by the • Failure to thrive
color flow mapping of the regurgitant jet into the • Recurrence of rheumatic fever worsens the stenosis
LA ). It also differentiates the eccentric regurgitation • Infective endocarditis, Atrial fibrillation and
(from cleft mitral valve) and central regurgitation thromboembolism are rare in children
(associated with annular dilatation) • Haemoptysis—long standing pulmonary venous
hypertension
Treatment:
Medical Treatment
• Prevention of endocarditis/prevention of rheumatic 13.11.3 Aortic stenosis (AS)
recurrence
• If CCF develops—antifailure measure (Digoxin/Diuretics) • The stenosis can occur at the level of the valve, above
(supravalvular) or below (subvalvular) the valve.
• Atrial fibrillation—rare (Digoxin is indicated).
• Valvular AS is more common than subvalvular AS.
Surgical Treatment:
Types
• Valve repair surgery preferred over valve replacement
as anticoagulant is not necessary in the former • Valvular AS is usually caused by bicuspid aortic valve
(with fused commissure and eccentric orifice).
• Valve repair surgery is indicated in
j Symptomatic patients with congenital MR • Sub valvular AS also have other associated cardiac
j Asymptomatic severe congenital MR with LV anomaly like VSD, PDA, Coarctation of aorta.
dysfunction • Supra valvular AS is often seen in Williams
j Intractable CCF, progressive cardiomegaly with Syndrome.
symptoms and pulmonary hypertension Clinical features:
• The eccentric regurgitation requires cleft repair • Most children with mild AS are asymptomatic
and the central regurgitation requires annuloplasty • Critical AS in neonates needs immediate
(commissuroplasty). intervention.
• Valve replacement surgery: • Effort intolerance, chest pain and sudden death can
j Rarely done with Bjork–Shiley tilting disk, St. Jude occur in severe AS. Pulse pressure can be narrow in
valve (with warfarin and aspirin ) or bio prosthesis severe AS.
(aspirin alone). • Features of Williams’s syndrome like elfin facies, cock
j Complication: Postoperative CCF tail party personality can be seen.
215
mebooksfree.com
• The cardiac findings (Fig. 13.12) are Surgical:

j Systolic thrill in right upper sternal border or • Closed aortic valvulotomy is done in patients with
carotids. failed balloon valvuloplasty.
j Grade 2 to 4/6 mid systolic murmur, best heard • Norwood procedure is preferred for critical
at the 2nd right ICS transmitting to apex and neonatal AS.
neck. • Other procedures like aortic valve commissurotomy,
j S2 is narrowly split and paradoxically split in aortic valve replacement or Ross procedure are done
severe AS. for patients with valvular AS.
j High pitched diastolic decrescendo murmur of Complications:
aortic regurgitation can be found in AS due to • Angina and effort intolerance.
bicuspid aortic valve. • Sudden cardiac death.
Investigations:
• The ECG shows LVH. 13.11.4 Aortic regurgitation (AR)
• Chest X-ray shows dilated ascending aorta and
prominent aortic knob. Cardiomegaly usually does • Can be congenital or acquired
not occur. • The rheumatic origin is commonest cause of acquired
• ECHO with Doppler study is required to form and it is almost always associated with mitral
categorise Aortic Stenosis as mild, moderate valve disease. There is a left ventricle volume over
and severe. load as the LV needs to handle volume both from the
left atrium and also from the aorta (leaked back due
Treatment:
to regurgitation).
Medical: • Causes of Congenital AR are
• Critical neonatal AS requires stabilization with j Congenital bicuspid aortic valve
prostaglandin E1 and inotropes before balloon j Association with sub pulmonary VSD
valvuloplasty. j Due to dilated aortic root—Marfans syndrome,
• Serial ECHO—Doppler alone without limitation of Ehlers Danlos syndrome
activities is needed for mild AS. j Post balloon dilation of aortic valve
Figure 13.12 The auscutatory findings in Aortic Stenosis (AS).

216
mebooksfree.com
Clinical features: • ECHO shows LV diastolic dimension increased in

• Cases are usually asymptomatic or may have mild proportion to the severity of AR and the LA remains
exercise intolerance. normal.
• Wide pulse pressure (systolic pressure is increased
since the stroke volume is increased, diastolic pressure Treatment:
is decreased due to leak from aorta to left ventricle) Medical:
and bounding water hammer pulse (due to increase • Dental hygiene/prevention of endocarditis or
in stroke volume in the aorta) are characteristic rheumatic recurrence
physical findings. • Activity needs to be restricted in severe cases.
• Findings on examination • ACE inhibitors to reduce LV dilatation and
j Precordium is hyperdynamic with lateral hypertrophy with AR.
displacement of apical impulse • If CCF appears—Digoxin, Diuretics, after load
j Diastolic thrill at left 3rd ICS reducing agents
j S1 is diminished with severe AR and S2 is usually
Surgical:
normal (Fig. 13.13).
• The Aortic valve repair is favored when compared
j A high pitched diastolic decrescendo murmur,
to valve replacement
best heard at 4th ICS, with patient sitting and
• Pulmonary Root autograft (ROSS procedure) is done
leaning forward and the duration of murmur
in selected young adults.
corresponds to the severity of AR.
• The indications for surgery are
j A systolic murmur in the 2nd right ICS due to
j Symptomatic (angina, syncope/dyspnea) with
relative AS.
severe AR
j In severe AR, a low pitched “Austin Flint murmur”
j Asymptomatic patients with progressive LV
(mid diastolic rumble) is heard at the apex. This may
enlargement
be due to regurgitant jet hitting anterior mitral leaflet.
• CCF is the most common postoperative
Investigations: complication.
• The ECG shows LVH and in long standing case there
may be additional LAH. Complications:
• Chest X-ray shows cardiomegaly, dilated ascending • Angina, CCF, premature ventricular contractions
aorta and prominent aortic knob. • Infective endocarditis is rare
Figure 13.13 The auscutatory findings in Aortic Regurgitation (AR).
217
mebooksfree.com
• To establish the diagnosis of previous streptococcal

13.12 Acute rheumatic fever (ARF) infection.
j Anti Streptolysin O antibody—Increased in 80%
Definition: of ARF and 20% normal individual, 67% patients
with isolated chorea. At least 320 todd units in
• ARF is delayed, nonsuppurative sequelae of upper
children and 250 todd units in adults is considered
respiratory tract infection caused by Group A beta—
positive.
hemolytic Streptococci (GAS). It affects joints, skin,
Anti DNAase B—titres of 240 Todd Units in
subcutaneous tissue, brain and heart. Except heart
j
children and 120 Todd Units in adults. Peak values

involvement, all others are reversible, requiring
seen between 3–6 wks.
only symptomatic therapy during the acute
Throat culture—Throat culture positive only in
episodes.
j
20%–30% (Positive throat culture is less reliable

Epidemiology
than antibody test for GAS).
• The prevalence of acute rheumatic fever in Indian
population varies from 0.5/1000 to 11/1000 in • To assess cardiac status.
various studies. ECHO—
• The disease occurs exclusively during childhood j To know severity of valvular involvement—
(5–15 year) stenosis/regurgitation.
• Males and female are equally affected. j Gross prolapse of mitral valve, or posterolateral
• Attack rate of ARF after GAS throat infection (not central) mitral regurgitation jet.
(types 1,3,5,6, and 18) varies with severity of j Chamber function and enlargement.
infection. j Coexisting PAH
• Overcrowding, poor socio economic status has j Presence of Pericardial effusion
increased the prevalence of throat infection in Chest X-ray (cardiomegaly suggest severe carditis)
children. Electrocardiogram (ECG)—prolonged PR interval, ventri-
Etiopathogenesis cles and left atrial enlargement.
• Delayed, non-suppurative sequelae of Group A Beta Diagnosis:
hemolytic Streptococcal pharyngitis. Revised jones criteria—1993 (Updated 2015)
• Molecular mimicry theory—M proteins of GAS
(M1, M5, M6, and M19) and myocardial proteins
like myosin.
j Mean latent period between the sore throat and Major criteria Minor criteria
clinical manifestations is 18 days (Range: 7–35 1. Pan carditis a) Clinical
days). 2. Polyarthritis 1. Fever > 38.5°F
j In chorea latency may be long (2–6 months) 3. Chorea 2. Polyarthralgia (in the
• Skin infection does not lead to ARF. Possible reasons 4. Subcutaneous absence of arthritis as
could be nodule major criteria)
j Less antibody response to GAS infection of skin. 5. Erythema b) Laboratory
j Neutralization of streptococcal toxins by skin marginatum 3. Elevated acute phase
lipids. reactants (ESR, CRP)
• Valvular involvement—Mitral valve is more affected 4. ECG: Prolonged PR
than aortic, tricuspid and pulmonary valves. interval > 0.16 s (in the
• Aschoffs bodies in the atrial myocardium is absence of carditis as
pathognomonic of ARF. major criteria)
Clinical features (Table 13.3): Essential Criteria—Supportive evidence of preceding
streptococcal infection
• History of streptococcal pharyngitis 1 to 4 weeks
before the onset of symptoms is usually present. 1. Positive throat culture or rapid streptococcal anti-
Other features like pallor, easy fatigability, malaise, gen test (Streptozyme test)
epistaxis, and abdomen pain may be seen. 2. Elevated or increasing streptococcal antibody
titer
Investigations
a. Anti streptolysin O (ASO titer: >333 unit for
• To detect presence of inflammation/ rheumatic children and >250 for adults)
activity.
b. Antideoxyribonuclease B ((Normal values
j ESR—Always elevated in Acute Rheumatic Fever 1:60 unit in preschool, 1:480 units in school
j Abnormal ESR > 60 mm/1 h in Rheumatic Fever children & 1:340 in adults)
j CRP—A value more than 6 mg/dL is diagnostic.
218
mebooksfree.com
Table 13.3 Clinical features of ARF
Clinical Specific term

feature and incidence Characteristics
Arthritis Migratory • Earliest, Least specific, Large joints (ankle, knee, wrist, elbow) affected
polyarthritis simultaneously/succession.
Overall incidence • Swelling, pain, warmth, severe tenderness and limited motion of joint. No residual
75%. deformity.
• Response to salicylates is dramatic.
• Consider alternate diagnosis if no resolution of symptom after 48 hours of
salicylates.
Carditis Pancarditis 1. Pericarditis:
Clinical—50% Chest pain, Pericardial Rub, Pericardial effusion (never tamponade)
Echo—90% Myocarditis:
a. Resting tachycardia (look for sleeping PR) or disproportionate tachycardia for
fever
b. Soft S1, S3 gallop
c. Cardiomegaly, CHF is more common in recurrence.
d. Myocardial contractility is not impaired and serum level of troponin not elevated
2. Endocarditis:
a. Mitral systolic murmur—Pan systolic murmur of MR
b. Mitral diastolic (Carey Coombs) murmur with no presystolic accentuation.
c. Aortic diastolic murmur.
– 80% of carditis occurs within first 2 wks.
– Rheumatic carditis lasts for 8-12 wks in 95% of cases.
Chorea Sydenham’s Delayed clinical manifestation (3-6 months)
Chorea • Pre pubertal girls are more affected.
St. Vitus Dance • Irregular, non-repetitive, quasi purposive involuntary movements—can last for
15% 18 months.
• Usually proximal, but may affect fingers, hands, face.
• Emotional lability, hypotonia are commonly present
• Pronator and spooning sign, darting tongue, milk maid’s grip,
• Jerky speech.
Subcutaneous 2%–10% • Hard, painless, freely mobile, non-pruritic 0.5–2 cm swelling, better seen than felt.
nodules • Extensor aspects of bony prominences, back, occiput, scapula.
• Non tender, almost always associated with carditis.
• Seen more during recurrence.
Erythema <10% • Red macules with serpengineous margins, are non-pruritic, annular and often
marginatum involves trunk and inner upper arm, never in face, evanescent accentuated by
warming the skin
Diagnosis: Exceptions of Jones Criteria:

2 Major Criteria • Chorea
Or • Indolent Carditis
1 Major and 2 Minor criteria • Recurrences of ARF
Plus Recent changes by American Heart Association 2015.
Essential criteria. 1. Categorizing the population as low risk (incidence <
• 2 major is more specific than 1 major and 2 minor 2 per 100000 school children per year or prevalence
manifestations. of RHD < 1 per 1000 population) and high risk
• Arthralgia should not be taken as minor criteria in the (most developing countries).
presence of arthritis. Prolonged PR interval should 2. Different criteria for both populations.
not be taken as minor criteria if carditis is present. 3. The major manifestation—Carditis now includes sub
• History of sore throat without substantial lab support clinical evidence of carditis (ECHO evidence of MR
is not adequate evidence of GAS infection. valvulitis without murmur) in high risk population.
219
mebooksfree.com
4. Major manifestation of poly arthritis, now Specific measure:

includes mono arthritis (in the absence of prior Control of inflammation with Anti-inflammatory
antiinflammatory drugs). agents:
5. Minor manifestation of polyarthralgia now • Total duration of antiinflammatory therapy—
includes monoarthralgia and poly-arthralgia can be 12weeks
considered as major manifestation after excluding • Aspirin and steroids are primarily used to control
other causes. inflammation. Naproxen and methylprednisolone
6. Other changes in the minor manifestation like fever can be used alternatively.
decreased to at least 38°C, ESR decreased to 30 mm/h Drugs for control of inflammation in acute rheumatic
and CRP at least 3 mg/dL in moderate /High risk fever:
populations (Developing nations).
7. In high risk population—recurrence of rheumatic Arthritis ± Responders: Aspirin—Starting
fever can be made with 3 minor manifestations alone. mild carditis doses: children 100 mg/kg/day for
2–3 weeks once symptoms resolved,
Other Terminologies: taper to 60-70 mg/kg/day
Recurrence in 2 minor criteria + supportive If aspirin intolerance detected—
a patient with evidence ( previous streptococcal Naproxen—10–20 mg/kg/day
established throat infection ). If no response to aspirin in four
heart disease: days—Switch over to steroid. After
ruling out chronic inflammatory/
Recurrence New episode of ARF following
myeloproliferative disorders.
another GAS infection; within 8
week of stopping çtreatment. Moderate Responders: Steroids; Prednisolone:
to severe 2 mg/kg/day, maximum 80 mg/day
Rebound Manifestations of rheumatic fever
carditis or till ESR normalizes –usually 2 weeks.
occurring within 4–6 weeks of
CCF Taper over 2–4 weeks, reduce dose by
stopping treatment or while tapering
2.5–5 mg every 3rd day. Start aspirin
the anti-inflammatory drugs.
50–75 mg/kg/day simultaneously, to
Relapse Worsening of ARF features complete total 12 weeks
during the treatment and often Nonresponders: IV methyl predni-
with carditis. solone 30 mg/kg/day for 3 days
Sydenham Sedative like phenobaribital, halop-
Differential Diagnosis:
chorea eridol or chlorpromazine if pheno-
• Juvenile Idiopathic Arthritis (JIA): Feature which barbital is ineffective
points towards JIA are
j Peripheral small joint involvement
Treatment of group A streptococcal infection (GAS)—
j Symmetrical large joints without migratory
and secondary prevention drugs.
involvement
j Pallor of joint Pharyngotonsil- Secondary
j No evidence of preceding streptococcal infection litis treatment prophylax-
j No response after 2 days of salicylates Drugs Dose (duration) is (interval)
• Other DDs: Systemic Lupus Erythematous, Reactive
arthritis, Septic arthritis, Parvo/hepatitis B arthritis, and Benza- 1.2 million Single dose 21 days
thine unit (>27 Kg)
Leukemia.
Penicil- after sensitiv-
Treatment: lin G ity test (AST)
• Principles of treatment: (deep IM 0.6 million Single dose 15 days
j Treatment of group A streptococcal infection. inj) unit (<27 Kg)
j Control of inflammation with anti-inflammatory
drug. Peni- children: 10 days Twice a day
cillin-V 250 mg qid 10 days Twice a day
j Treatment of complications.
(oral) adult: 500 mg
• General measures and symptomatic relief: tid
j Analgesics for pain relief (Aspirin should be
avoided till diagnosis is confirmed). Erythro- 20 mg/kg/ Not recom- Twice a day
j Indications for Hospitalization is needed for mycin dose max mended
(oral) 500 mg
– Moderate to severe carditis
contraindica-
– Severe arthritis
tion: liver
– Chorea.
disorder
j Rest is individualized according to symptoms.
220
mebooksfree.com
Prevention:
Congenital Causes Acquired Causes
• Primary Prevention:
j 10 day course of Penicillin. Age Cause Age Cause
j 30% have sub clinical pharyngitis, hence may not
seek medical treatment. 1st week Transposition of 1 to 4 Kawasaki disease
j 30% develop ARF without symptoms of great vessels years
PDA (premature)
streptococcal pharyngitis.
TAPVC
• Secondary Prevention: AS, PS
j Chronic antibiotic therapy in confirmed cases to
prevent secondary steptococcal infection 1–4 Coarctation of >5 Rheumatic Heart
Duration of secondary prophylaxis weeks aorta, years Disease
Large (VSD, PDA) Thyroid diseases
No carditis 5 years/21 years of age, in preterms Cardio Myopa-
whichever is longer thy
Mild to moderate carditis 10 years/25 years of age, Drugs (doxoru-
and healed carditis whichever is longer bicin)
Severe disease or post Lifelong. One may opt 4–6 Enodcardial cush- Others Muscular dys-
intervention patients for secondary prophy- weeks ion defect trophy
laxis up to the age of 40 VSD(large) Hypoxia, hyper-
years 6 VSD tension (AGN)
weeks–4 PDA Hypoglycemia,
months acidosis, hypoc-
alcemia,
13.13 Congestive cardiac failure (CCF) Heart blocks
• Clinical syndrome characterized by inability of the Diagnosis:

heart to pump enough blood to meet the demands of
the body, to maintain systemic or pulmonary venous • There is no single test to diagnose CCF.
return adequately or both • History of poor feeding (suck rest suck cycle), fore head
sweating in infants. Dyspnea on exertion, easy fatigue,
Pathogenesis:
puffy eyelid, and swollen feet is seen in older children.
• The following laws explains the pathophysiology of CCF • Findings on examination are,
j Frank–Starling Law—Ventricular end diastolic j Compensatory mechanism—tachycardia,
volume (preload) increases cardiac output cardiomegaly, perspiration.
j Laplace Law—Wall tension = Pressure × radius/2 j Pulmonary congestion—tachypnea, dyspnea,
× wall thickness orthopnea, PND, lung crept.
Compensatory neurohormonal mechanism: j Systemic congestion—hepatomegaly, puffy eyelid,
• Sympathetic: distended neck vein.
j Action = Increase in epinephrine/Nor Epinephrine • The chest radiography shows Cardiomegaly,
→Increased Heart Rate/ Contractility → Increased • ECG used to find the cause
Cardiac output • Echo shows LV dysfunction
j Adverse effect = Increased afterload, hyper Treatment: Aim of the treatment is to
metabolism, arrhthmogenicity and myocardial toxicity
• Renin Angiotensin aldosterone: • Eliminate cause (Thyroid, Congenital Heart Disease,
Hypertension, Fever, Infection)
j Decreased Renal Blood Flow → Increased
renin→ Increased Angiotensin II → Myocardial • Treat contributing factor(Anemia, Arrhythmias)
hypertrophy/fibrosis • Control failure features
Etiology: Age wise causes of CCF in children General measures:
• Infant seat (head end elevation)
Congenital Causes Acquired Causes • Oxygen supplementation
• Providing adequate calories (160 kcal/kg/day)
Age Cause Age Cause
• Salt restriction (<0.5 gm/day)
At birth Hydrops fetalis 1yr Viral myocarditis • Bed rest
Hypoplastic Left Anemia Specific measures:
Heart Syndrome, Supra Ventricu-
• Diuretics: to decrease preload and decrease
Volume overload lar Tachycardia congestion but they don’t improve myocardial
(TR,AR, AV fistula)
contraction
221
mebooksfree.com
j E.g., Loop—Furosemide (2–3 mg/kg/day 3 div

dose) or Thiazide and Spironolactone 13.14 Hypertension
j (Adverse effect—hypokalemia, hypochloremic
alkalosis) • Definition: Hypertension is defined as “average
• Digoxin systolic and/or diastolic pressure >95th percentile
j Mechanism of action—increase myocardial for gender, age and height on >3 occasions.”
contractility, parasympathomimetic and Prehypertension is defined as “average systolic or
diuresis. diastolic pressures between 90–95th percentile for
gender, age and height.”
Digitalising and maintenance dose of Digoxin • The prevalence of hypertension is 1%–3% and
Total digitalising Maintenance prevalence increasing due to the increased prevalence
Dose (µ/kg/dose) (µ/kg/dose) of obesity. The prevalence of persistent secondary
hypertension is 0.1% and is commonly due to renal
Premature 20 5
disease.
Term 30 8
Etiology
2years 30 10
• Primary (Essential) or secondary due to a definable
• Digitalisation: Per Oral or Intra Venous (severe cause. Most common cause of hypertension is
CHF) but no intra-muscular doses.
glomerulonephritis and chronic hypertension is
• Baseline ECG (PR interval, rhythm, hypokalemia,
commonly associated with renal parenchymal
hypercalcemia can precipitate toxicity)
disease.
• Administration
j =1/2 (Total digitalising dose) stat
Age wise causes of hypertension in children
j 1/4 (Total digitalising dose) after 6 h
j 1/4 (Total digitalising dose) after 12 h

Age group Common causes
• 12 h after digitalizing dose take ECG, and then give
the maintenance. Newborn Renal artery thrombosis,
• Effects on ECG—Ventricular Repolarisation, renal artery stenosis,
ST depression congenital malformation,
• Other adverse events—anorexia, vomiting, fatigue, coarctation of aorta.
visual disturbances Infancy—6 years Renal parenchymal disease,
• Sr. Digoxin therapeutic levels 0.8 to 2 ng/mL coarctation of aorta, renal
artery stenosis.
6–10 years Essential hypertension,
• After Load Reducing Agents: renal artery stenosis, renal
j Arteriolar dilator—hydralazine, parenchymal disease.
j Venodialator—GTN, Isosorbide di nitrate Adolescence Essential hypertension, renal
j Mixed—ACE inhibitors, prazosin parenchymal disease.
• Other Drugs:
j Rapid acting ionotropic—amrinone,
j β Blockers—Carvedilol, metoprolol (muscular Clinical features—symptoms and signs
dystrophy, post myocarditis cardiomyopathy) • Hypertension is usually silent or can present as
j Carnitine (Dilated cardiomyapathy) congestive cardiac failure in children.
• Surgical Management: Cardiac transplant for end- Causes of hypertension in children and its features
stage HF secondary to cardiomyopathy, hypoplastic
left heart syndrome, failure of Fontan and palliated Cause Clinical features
congenital heart disease
Glomerulonephritis Headache, vision
Recent drugs used in CCF changes, nose bleeds, or
• Calcium Sensitizing drugs—Levosimendan, nausea, edema, oliguria,
Pimobendan hematuria.
• Nesiritide (Recombinant human B-type natriuretic Coarctation of the aorta Blood pressure difference
peptide) between the upper and
• Vasopressin receptor antagonist—Dual (V1a&V2): lower limb.
Conivaptan, SelectiveV1: Relcovaptan Selective V2: Neurofibromatosis Café-au-lait patches, Skin
Tolvaptan. nodules
• Metabolic modulator—Perhexiline
Polycystic kidney disease Abdominal masses
222
mebooksfree.com
Commonly used antihypertensive drugs in children

Cause Clinical features
Connective tissue Presence of joint pains, Drug Initial dose
disorders rash and systemic
symptoms. Hypertensive emergencies
Pheochromocytoma Sweating, Headache, Nifedipine 0.25 mg/kg
tremors and palpitations Sodium nitroprusside 0.5 µg/kg/min IV
Labetalol 1 mg/kg/hr IV, can be
• Signs and symptoms of cardiomegaly, hypertensive given as bolus or steady
retinopathy or neurological involvement are important, infusion
since they indicate long standing hypertension. Long-term therapy
Feature of “Syndrome X”—hypertension, obesity, Enalapril 0.15 mg/kg/day
hyperlipidemia and diabetes mellitus. Extended-release nifedipine 0.25 mg/kg/day
Diagnosis: It depends on the stage of hypertension, If
Furosemide 1 mg/kg/day
• Stage 1 (BP is between 95th to the 99th percentile
plus 5 mm Hg) then BP should be repeated on 2
more occasions. Target blood pressure
• Stage 2 (BP is >99th percentile plus 5 mm Hg), start • BP <95th percentile for gender, age and height—In
stepwise evaluation and therapy. uncomplicated primary hypertension
• BP <90th percentile for gender, age and height—
Step 1: Initial evaluation—Full blood count, Serum In cases of chronic renal disease, diabetes, or
electrolytes, Uric acid, Renal function tests, Lipid hypertensive target-organ damage
profile, Fundus examination, Urinalysis, culture and
Surgery-balloon angioplasty for renal artery stenosis or in
Renal ultrasound.
pheochromocytoma.
Step 2: Additional Tests—Echocardiography, Nuclear
Complications:
scans—DMSA, Captopril renography, DTPA diuretic
scan, Doppler ultrasound of renal arteries, Thyroid • Hypertensive emergencies
Severe hypertension with life-threatening or organ-
profile, Urinary catecholamine, Plasma aldosterone
j
threatening complications,
and plasma renin activity, urine steroids, MIBG
Includes encephalopathy (seizures, stroke, focal
scan, and Renal arteriography/DSA (after urinary
j
deficits), acute heart failure, pulmonary edema,

catecholamine exclude pheochromocytoma).
dissecting aortic aneurysm or acute renal failure.
Step 3: Screening—Low plasma high-density lipoprotein
Sublingual nifedipine is the initial treatment of
cholesterol, elevated plasma triglyceride and
j
choice before establishing an intravenous line.

abnormal glucose tolerance. Screening—history of
IV sodium nitroprusside or labetolol infusion is
hypertension in family members, those who are
j
started with a goal of reducing the blood pressure

obese, IUGR or have urinary infections and renal
over a 24-h period.
scars.
Treatment: • Hypertensive urgencies
A) Nonpharmacologic methods: Life style • This condition is where complications is less but BP
needed to be reduced within 24 h.
modifications like
j Weight reduction • E.g., Acute Glomerulo–Nephritis, accelerated
hypertension following renal transplantation.
j Exercise
j Dietary intervention—Salt reduction
(Recommended sodium intake is only 1.2 g/day
for 4–8-years and 1.5 g/day for older children) 13.15 Infective endocarditis (IE)
B) Pharmacologic method:
Indication: Definition
Symptomatic hypertension
• Infective endocarditis is defined as infection
j
j Secondary hypertension
of endocardium lining the heart valves, mural
j Hypertensive target-organ damage
endocardium and blood vessels.
Diabetes and Persistent hypertension despite
Etiopathogenesis
j
compliant nonpharmacologic methods.

• The most common organisms are Viridans
Anti hypertensive Drugs—Drug of choice depends on the streptococci (α-hemolytic streptococci) and
efficacy, dosing availability, frequency, adverse effects and Staphylococcus aureus. The viridans group of
cost of the drug. streptococcal organisms are common following
223
mebooksfree.com
dental procedures. The Staphylococcal endocarditis grade fever , loss of weight and appetite , myalgia,
can occur without underlying heart disease in IV drug arthralgia, and easy fatigability
abusers and post-operative children. • Physical examination findings
• Other organism include j Heart murmurs—new or changing intensity of
j Group D enterococci in cases involving murmur.
manipulation of large bowel or genitourinary j Fever—101–103°F.
tract j Splenomegaly
j Fungal endocarditis in sick neonate and long j Dermatological finding—due to embolization/
term antibiotic/steroid therapy. immune phenomenon.
j Coagulase-negative staphylococci in cases of j Petechiae—mucus membrane/skin, Splinter
indwelling central venous catheters. hemorrhage, Janeway lesion, Oslers nodes
j HACEK group organisms (Haemophilus, j Pulmonary emboli (in VSD, PDA), CNS emboli—
Actinobacillus, Cardiobacterium, Eikenella, seizures/focal neurological deficit (in aortic/mitral
Kingella species). valve disease), Roth’s spots, hematuria.
• Culture negative endocarditis is a condition where j Caries tooth, clubbing of finger, appearance of new
there is clinical and ECHO evidence of endocarditis signs of CCF.
but the culture is negative. • Lab studies:
j The common causes are recent use of antibiotic, j Positive blood culture is seen in more than 90%
infection with fastidious organisms and fungal of cases and previous antibiotic use decreases the
endocarditis. yield to 40%.
Pathogenesis (Fig. 13.14) j Three separate blood samples for culture in 24 h;
• The two main prerequisite to develop infective If no growth in second day, 2 more cultures can be
endocarditis are damaged endothelium and obtained.
bacteremia. j No more than 5 cultures in 2 days are advisable
• The common causes of damaged endothelium (3 mL in infant, 5 mL in children).
are congenital heart aisease (TOF, VSD, Aortic j CBC shows anemia,thrombocytopenia and raised
valve disease, Rheumatic MR, MR with MVP) and ESR.
endothelial damage occurs along the low pressure • ECHO—shows the site of infection, extent of valve
side of the defect/around the defect/side of the jet damage and cardiac function.
impingement. j Transesophageal ECHO are more sensitive
• The common causes of bacteremia are chewing with than trans thoracic ECHO in LV outflow tract
diseased teeth and gums. endocarditis, aortic root abscesses, rupture of sinus
Diagnosis: of valsalva and postcardiac surgery.
• History—Underlying heart disease, tooth ache or j False Negative Echo—may suggest small or already
dental procedure , tonsillectomy, prolonged low embolised vegetation
Figure 13.14 The pathogenesis of infective endocarditis.

224
mebooksfree.com
j False positive—anatomical change in valve, MRSA is suspected then vancomycin instead of

myxomatous change in valve or sterile thrombus. penicillin is used.
j Vegetation in ECHO persists even months after • Final antibiotic choice depends on blood culture
bacteriological cure of Infective endocarditis. antibiotic sensitivity test.
Duke Criteria help in the diagnosis of endocarditis. Drug of choice for different organisms in infective en-
docarditis
Major criteria include
1. Positive blood cultures (two separate cultures for a Modification
usual pathogen, two or more for less typical patho- Organism Treatment if necessary
gens, or single blood culture for coxiella burnetii/
Native Valve En- IV penicillin/ IV penicillin/
IgG antibody >1:800) and
docarditis Caused ceftriaxone for ceftriaxone +
2. Evidence of endocarditis on echocardiography
by Highly Peni- 4 weeks Gentamycin
(intracardiac mass on a valve or other site, regurgitant
cillin-Susceptible for 2 weeks
flow near a prosthesis, abscess, partial dehiscence of
Viridans Group
prosthetic valves, or new valve regurgitant flow).
Streptococci and
Minor criteria include Streptococcus bovis
1. Predisposing conditions/IV drug user Therapy for En- Methicillin Methicillin
2. Fever> 38°C docarditis Caused sensitive Resistant
3. Embolic-vascular signs (major arterial emboli, by Staphylococci Semisynthetic vancomycin
septic pulmonary infract, mycotic aneurysm, intra in the native valve β lactamase for 6 weeks
cranial Hemorhage, conjunctival hemorrhage, Penicillin for with or with-
janeway lesions) 6 weeks with out gentamy-
4. Immune complex phenomena (glomerulonephri- or without cin for 5 days
tis, arthritis, rheumatoid factor, Osler nodes, Roth gentamycin
spots) for 5 days
5. A single positive blood culture or serologic evi-
Therapy for En- Ampicillin + Penicillin al-
dence of infection, and echocardiographic signs
docarditis Caused gentamycin lergy—replace
not meeting the major criteria.
by enterococci in for 6 weeks with vanco-
The following were added to modified Dukes criteria the native valve mycin
1. Presence of newly diagnosed clubbing, splenomeg- HACEK organism Ceftriaxone
aly, splinter hemorrhages, and petechiae alone or
2. A high erythrocyte sedimentation rate Ampicillin +
3. A high C-reactive protein level gentamycin
4. Presence of central nonfeeding lines, peripheral for 4 weeks
lines, and microscopic hematuria.
Fungal Amphotericin
endocarditis B
Prosthetic valve Treated for 6
• Terminologies: weeks
j Definite endocarditis (IE) Presence of Two major
criteria or one major and three minor or five
minor criteria
j Possible IE: Presence of 1 major + 1 minor, 3 • Surgical treatment: Indications are
Minor j Progressive CCF
j Rejected Endocarditis when a firm alternative j Malfunction of prosthetic valve
diagnosis explaining the features of IE is present. j Positive blood culture positive even after 2 weeks
of antibiotics
Treatment:
Bacteriological relapse cases
• Medical Treatment: The antibiotic therapy should
j
be instituted immediately once a definitive diagnosis Infective endocarditis prophylaxis:

is made and a total of 4–6 week of treatment is • Antibiotics before various medical procedures
recommended. (dental manipulation, colostomy, etc.) may reduce
• In non-staphylococcal disease, bacteremia usually the incidence of infective endocarditis in susceptible
resolves in 24–48 h, whereas fever resolves in 5–6 days patients
with appropriate antibiotic therapy but resolution • Appropriate dental care and oral hygiene
with staphylococcal disease may take longer. Regimen:
• Initial empirical antibiotic is antistaphylococcal • Drugs started orally 1 h before or 30 min
semisynthetic penicillin + aminoglycoside and if (intravenously) before the procedure
225
mebooksfree.com
• Dental, oral, respiratory, esophageal procedures: • A pericardial friction rub (high-pitched scratchy
Amoxicillin or ampicillin 50 mg/kg (if allergic to sound present during both systole and diastole) is
Penicillin then Cephalexin 50 mg/kg ) pathognomonic of acute pericarditis.
• Genitourinary/gastro intestinal procedures: Ampicillin • The heart sounds may be muffled. Tachycardia is
50 mg/kg + Gentamicin 1.5 mg/kg within 30 minutes an important sign and may indicate impending
of starting the procedure then 6 hours later. tamponade. Dullness to percussion in the scapular
region due to compression of the left lung may be
seen in patients with large effusions (Ewart’s sign).
13.16 Acute pericarditis Investigations

• Acute phase reactants—ESR elevated.
• Chest radiography may reveal a water-bottle
Definition: appearance of the heart with normal pulmonary
• Inflammation of the pericardial space and the origins vascularity (Fig. 13.15).
of the great vessels. They were classified into 3 types • ECG shows (A) low-voltage QRS complexes, (B)
based on the duration of onset ST segment changes, (C) electrical alternans, an
j Acute if onset within 6 weeks alternation in amplitude of the complexes with each
j Subacute if onset within 6 weeks to 6 months cardiac cycle resulting from rotational motion of the
j Chronic if onset more than 6 months heart floating in the pericardial fluid.
Etiology • Echocardiography—Echo-free space around the
• Viral infections are the most common causes. heart.
Tuberculosis (TB) pericarditis may be associated • Pericardiocentesis—Done in cardiac tamponade,
with HIV infection. suspected purulent pericarditis, large pericardial
• Purulent pericarditis (Primary bacterial pericarditis— effusions unresponsive to pharmacological
Staphylococcus aureus, Haemophilus influenza type B, interventions, unexplained effusions when present for
Neisseria meningitides is the most common bacterial more than 3 months and when tuberculosis is suspected.
organism/hematogenous extension of existing Management
pulmonary, cardiac, hematologic or sub diaphragmatic • Viral pericarditis: Generally resolves spontaneously
infection )- Tamponade is far more likely to occur in in 4–6 weeks. Bed rest for 1 week and analgesics are
purulent pericarditis. Other causes are recommended.
• Autoimmune and connective tissue disorders • Tuberculous pericarditis. Antituberculous therapy
• Invasive procedures, trauma or radiation therapy. along with steroids
• Uremia (Blood urea nitrogen levels exceeding
60 mg/dL) can cause pericarditis
• Post pericardiotomy syndrome.
Pathophysiology
• Acute inflammation of the pericardium produces
serous fluid, purulent fluid or dense fibrinous
material. This may resolve spontaneously or
require minimal intervention, based on the
etiology.
• Acute collection of fluid in the pericardial space
increases intra-pericardial pressure and can affect
filling of the heart. Distended pericardium affects the
heart primarily during diastole, affecting the right
side more than the left side. This can result in cardiac
tamponade.
• If the process of inflammation continues and the fluid
organizes into a thickened coating around the heart it
results in constrictive pericarditis.
Clinical features
• Nonspecific prodrome of malaise, fever and chest
pain (precordial in location and pleuritic or dull
in nature. It is exacerbated by inspiration, cough,
motion, or recumbent posture, and relieved by Figure 13.15 Water bottle heart seen in pericardial
leaning forward). effusion.
226
mebooksfree.com
• Purulent pericarditis: Drainage of the pericardial fluid, Causes:

institution of appropriate antibiotics and intense • Most commonly they are Idiopathic
supportive care. Vancomycin and a third generation • 20% cases have associated Wolff–Parkinson–White
cephalosporin should be the initial antibiotics of syndrome which becomes evident after converting to
choice. 4 weeks of antibiotic therapy is required in sinus rhythm.
case of staphylococcus infection and 3 weeks for other • Other associated cardiac anomalies are
organisms. j Ebstein’s anomaly
• Postpericardiotomy syndrome: Relatively benign, j Single ventricle
self-limiting condition. Majority of the patients j Congenitally corrected TGA and following cardiac
respond to bed rest and anti-inflammatory agents. surgery.
Steroids/Methotrexate have been used for chronic Clinical features:
postpericardiotomy syndrome with recurrent • History of fever/drug exposure, pallor, irritability,
pericardial effusions. tachypnea, poor feeding, chest pain, breathlessness,
light headedness and fatigue. SVT produces CCF if
sustained for more than 12 h. Canon waves—specific
13.17 Cardiac arrhythmia for reentrant tachycardia can present with neck
pulsations.
ECG findings:
• Suspect arrhythmia in the following conditions, Features to diagnose SVT are (Fig. 13.16)
j Unexplained Irregular heart beat rhythm.
j Disproportionate tachycardia for a clinical condition. • Rate SVT rate ≥180 in children, ≥220 in infants
j Unexplained cardiac failure or worsening of • Rhythm is rapid and regular
established cardiac condition. • Narrow QRS complex tachycardia
j Underlying cardiac anomaly known to be • with normal P wave morphology
associated with rhythm disorders (e.g., Ebsteins Management:
anomaly). • Vagal stimulatory maneuvers:
j History of unexplained Syncope, palpitations, j Infants: Ice water bag on face for 10 s to produce
chest discomfort with Family history of sudden diving reflex.
cardiac Deaths. j Older children: Unilateral carotid sinus massage,
• Initial steps in management based on gagging, pressure on eyeball and Valsalva
j Clinical presence or absence of hemodynamic maneuver
instability • Adenosine:
j QRS duration on the initial ECG j Treatment of choice in hemodynamically stable
• Based on the QRS duration, tachyarrhythmia is SVT
classified as narrow/wide. j Effective for all reciprocating SVT.
j Characteristic: negative inotropic, dromotropic,
chronotropic, short half-life <10 sec, minimal
hemodynamic consequence
13.18 Supra ventricular tachycardia j Method:
(SVT) – Draw up starting dose of adenosine—starting
50 µg/kg, with increments of 50 µg/kg every
1 to 2 min, to a maximum dose of 25 µg/kg.
• The Most common tachyarrhythmia in pediatric age
Draw up 10 mL saline flush
group with incidence of 1 in 250 to 1 in 1000.
– Administered as a rapid IV push followed by
Types:
flushing with saline
• AV reentrant/reciprocating tachycardia—Most
common type of SVT, which has 2 pathways,
j Anatomically separate by pass tract—bundle
of kent, producing accessory reciprocating AV
tachycardia, usually have Wolf–Parkinson white
preexcitation (WPW)
j Functionally separate by pass tract—dual AV
nodal pathway, producing nodal reciprocating AV
tachycardia
• Atrial tachycardia
• AV nodal/Junctional tachycardia Figure 13.16 ECG showing the features of SVT.
227
mebooksfree.com
– Repeat procedure every 2 min till tachycardia is • Preductal coarctation versus Postductal coarctation
terminated.
Events Preductal Postductal
– Confirm with 12 lead ECG
coarctation coarctation
• Emergency cardioversion (Coarctation (Coarctation
Indicated in Infants with severe CCF or if
is proximal to is distal
j
hemodynamically unstable ductus arterio- to ductus

j 0.5 joule/kg increased stepwise to 2 joule/kg sus) arteriosus)
• Radio frequency ablation/surgical interruption of
Fetal life • Collaterals • Collaterals
accessory pathway—if medical management fails
not formed formed
Other drugs: because co- because of
• Intravenous propranolol to treat SVT with WPW arctation is obstruction
• Intravenous Amiodarone—Postoperative atrial not obstruct- of flow in
tachycardia ing the flow descending
• Intravenous verapamil—Avoided in infants of upper and aorta
Prevention of recurrence of SVT lower limbs
• Maintenance drug therapy is started once sinus After birth • No collater- • Collaterals
rhythm is achieved (Ductus arte- als* are present
• Infants without WPW—Oral propranolol for 12 riosus closes • So symp- • So hyper-
months → Desceding toms ap- tension
• Infants with CCF and WPW—treat CCF with aorta receives pears early and CCF
digoxin then change to oral Propranolol once CCF blood from in life* does not
improves. left ventricle • Hyperten- occur early
via ascending sion in life
• Infants with WPW. Long term atenolol or aorta) • Congestive
propranolol, avoid digoxin, and verapamil.
heart failure
13.19 Coarctation of aorta (CoA) • Collaterals formed by—internal mammary artery,

intercostal artery, anterior spinal artery.
• Coarctation of aorta involves constriction of the aortic Clinical Presentation

lumen along with dilation in the immediate distal • Severe CoA presents within 6 weeks (closure
part. of PDA takes some time) of life with CCF and
• The location is described in relation to ligamentum differential cyanosis (associated PDA) and weak
arteriosum. femoral pulses.
j Preductal—coarctation is proximal to the • Absent murmur, single, and loud S2 are the
ligamentum or ductus arteriosus auscultatory findings of CoA in neonatal period.
j Post ductal—coarctation is distal to the • Weakness and pain in legs after exercise, incidentally
ligamentum or ductus arteriosus detected hypertension, disparity between upper
• Approximately 90% of CoA occurs just below the and lower limb pulsations (Radiofemoral delay)
origin of the left subclavian artery at the origin of the and blood pressure differences in the arms and legs
ductus arteriosus (juxaductal coarctation). are the other common presentations. The lower
• More common in males (2:1) and often associated limb pulses are weak (absent in 40% of patients)
with Turner syndrome. in contrast to the bounding pulses of the arms and
• The most commmon associated lesion is Bicuspid carotid vessels.
aortic valve (70% cases) and other associated lesions Diagnosis:
are TGV and intracerebral aneurysm. • ECG—Infants show RVH, while older children shows
Hemodynamics LVH.
• In fetal life, the descending aorta receives the blood • Chest X-ray:
from the ductus (right to left shunt). But after j “Fig. of 3 appearance” due to prestenotic dilation,
the ductal closure, the symptoms appear due to narrowing and post stenotic dilation
reduced blood flow through the aortic isthmus. If j “E sign” seen on contrast esophagogram, due to
the development of collaterals are poor, then these pressure on anterior wall of esophagus
clinical features of LV dysfunction appear early in life. j Notching of the inferor border of 3rd–9th ribs
On the other side if there are good collaterals, the from pressure erosion by enlarged collateral
infant goes asypmtomatic. vessels, usually seen beyond the age of 3 years.
228
mebooksfree.com
• ECHO: • Surgery is done after stabilisaton—Resection of

j Neonatal CoA—Aortic isthmus <3 mm without the coarctation with end to end anastomosis is the
PDA or <4 mm with PDA treatment of choice.
j Suprasternal notch view—shows posterior shelf • For recoarctation- balloon angioplasty is treament of
sign choice.
Treatment:
• Severe COA is duct dependent systemic circulation
defect and PGE-1 infusion can be life saving in such 13.20 Cardiovascular involvement
situation along with anti failure measure. in systemic diseases
Systemic Disease Pathophysiology Manifestation Treatment

Mucopolysaccharidoses Accumulation of • Regurgitation in the mitral and Treating underlying
glycoasminoglycans aortic valves condition
in the myocardium • Dilated cardiomyopathy
and coronary • Asymmetrical septal hypertrophy
arteries
Systemic Lupus Immune mediated • Pericarditis Active valvulitis needs
Erythematosus changes in all layers • Myocarditis steroids
of the heart • Libman-Sacks verrucous
endocarditis lesions in mitral valve
Rhematoid Arthiritis Infiltration of • Pericarditis – frequently with Severe pericarditis
inflammatory cells systemic onset JRA and rare in requires steroids
pauci articular JRA
• Myocarditis
Marfans syndrome • Distruption of • Dilatation of sinus of valsalva and Atenolol, enalapril
elastic media aortic root (thus AR) decrease the rate of
• Fibromyxoid • MVP, MR aortic root dilatation
degeneration of • Early death due to aortic
mitral valve dissection
Hypothyroidism • PDA, PS frequently seen Treating underlying
• Low QRS in limb leads condition
• Prologed PR/QT interval
• Dome shaped T wave “Mosque
sign”
• Pericardial effusion
• Hypertrophic cardiomyopathy
Duchenne’s Muscular Endocardial • Dilated cardiomyopathy ACE inhibitors and
Dystrophy thickening of the LV • RVH, RBBB B-blockers delay the
and LA improves LV function
229
mebooksfree.com
13.21 Miscellaneous cardiac

conditions
Cardiac condition Pathophysiology Manifestation Treatment

Anomalous Origin Left coronary artery arise • Features of anterolateral High mortality
of the Left Coronary from the pulmonary artery myocardial infraction Ligation of the anamolous
Artery from the (deep Q,ST elevation, artery close to PA
Pulmonary Artery inverted T waves in lead I Definitive surgery –
(ALCAPA syndrome) and aVL) Takeuchi repair
• Troponin I level
increased
DiGeorge syndrome Chromosome 22q11 • CATCH-22 (Cardia, Correction of cardiac
deletion syndrome Abnormal facies, thymic malformation
hypoplasia, Cleft palate, Calcium supplement
Hypocalcemia) Live vaccine contraindicated
• TOF Thymus transplant
• Interrupted aotic arch
• VSD
Scimitar syndrome Pulmonary veins from right • Associated anomalies— Ligation of the systemic
lower or middle lode drain ASD, PDA, left sided arterial supply to right lung
anomalously into the IVC obstructive lesions
• Dextrocardia
Patent Foramen Tunnel between septum Small left to right shunt Observation
Ovale (PFO) secundum and septum detected by color Doppler
primum

230
mebooksfree.com
Chapter | 14 |
Respiratory system
Clinical features:
14.1 Acute bronchiolitis • Usually follows an episode of upper respiratory
tract infection. Fever is mostly low grade
• Bronchiolitis is inflammation and narrowing (38.5–39°C)
of bronchial tree, secondary to acute lower • Fast breathing and decreased oral intake are
respiratory tract infection. Infants are commonly the typical presenting complaints. Severe cases
affected, but can also affect children upto 2 years may present with irritability, dyspnea and
of age. cyanosis. Apnea may be more prominent in
• More common in boys than girls. infants < 6 months old
• Usually occurs during winter and spring season • On examination, signs of respiratory distress
• Predominantly caused by Viruses including tachypnea, usage of accessory muscles,
• Risk factors increased respiratory effort indicated by nasal
j Chronic lung disease/Bronchopulmonary dysplasia flaring, tracheal tugging, subcostal and intercostal
j Formula fed Infants retractions are present
j Maternal smoking • On auscultation, fine crackles or overt wheezes, with
j Overcrowding prolongation of the expiratory phase of breathing
j Infants with preexisting smaller airway and diminished are often noticed.
lung function • Reduced breath sounds suggest varying degrees of
bronchiolar obstruction. Severe obstruction to airflow
Etiopathogenesis: can increase the severity of wheezing; In the presence
• Inflammation of the bronchiolar mucosa of increased work of breathing, reduced breath
• Edema, thickening, formation of mucus plug and sounds and absent wheezing (Silent chest) can
cellular debris indicate severe obstruction and impending respiratory
• Bronchiolar spasm, increased airway resistance and failure
reduction in airflow • Systemic symptoms are usually absent
• Diminished ventilation and diffusion DD’s
• Hypoxia and retention of carbon dioxide leading to • Foreign body aspiration
respiratory acidosis • GERD
Causes: • Congenital malformation of respiratory tract—
• RSV is responsible for >50% of cases. Vascular rings, Bronchomalacia
• Other Viral causes—Parainfluenza, Influenza, Diagnosis
Adenovirus, Human metapneumovirus, Human • Mostly clinical
bocavirus • Pulse oximetry may reveal hypoxia
• Bacterial causes—Mycoplasma pneumoniae, • Cell counts are usually normal
Hemophilus influenzae can cause similar illness
231
mebooksfree.com
• Approximately 2% cases progress to respiratory

failure and might require CPAP or assisted
ventilation
• Highest risk for respiratory compromise is during the
first 48–72 h
• Overall prognosis is very good.
• Case fatality < 1%. Death usually due to apnea,
respiratory arrest and severe dehydration
Prevention
• RSV immunoglobulin
• Palivizumab—Monoclonal antibody to RSV
• Can be used to decrease the severity in
j <2years of age with chronic lung disease
j Premature infants
j Congenital heart disease
Figure 14.1 Chest Xray of 1 year old child showing

bilateral hyperinflation and patchy perihilar infiltrates
characteristic of Acute bronchiolitis.
14.2 Acute tonsillopharyngitis
• Chest X-ray (Fig. 14.1)—Hyperinflation with patchy • Acute infection often involves both pharynx
infiltrates, atelectasis and reticulonodular pattern. and tonsils, hence termed as acute tonsillopharyngitis.
Changes are non-specific and does not differentiate Follows an episode of rhinitis or sinusitis in some
between viral and bacterial disease cases.
• Viruses are implicated in 80%–90% of cases
Management
and the remaining 10%–20% caused by
• Indications for hospitalization bacteria.
j Respiratory distress.
j Apnea Etiology
j Hypoxia • Viral
j Poor feeding/lethargic child j Adenovirus
j Comorbid conditions—Congenital heart disease, j Coronavirus
Chronic lung disease, Neuromuscular disease and j Enterovirus
Malnutrition j Rhinovirus
• Children with hypoxia should receive humidified j Respiratory syncytial virus
oxygen promptly. Frequent nasal and oral suctioning • Bacterial
relieves upper respiratory obstruction. j Group A β-hemolytic streptococcus
• Nebulization with hypertonic 3% saline and j Group C streptococcus
racemic epinephrine offers symptomatic relief. j Francisella tularensis
Epinephrine induced tachycardia often limits its j Mycoplasma pneumoniae
continuous usage. j Neisseria gonorrhoeae
• In severe cases, a trial of bronchodilators can be tried j Corynebacterium diphtheriae
and is often associated with short term response Clinical features
• Role of Corticosteroids is controversial and its • Cases present with fever, cough, sore throat, difficult/
routine use is not recommended painful swallowing and vomiting. Severe cases
• Antiviral Therapy: Aerosolized Ribavirin– Used in develop dysphagia and drooling of saliva. Enlarged,
children with congenital heart disease and chronic congested tonsils along with congestion of posterior
lung disease pharyngeal wall seen.
• Infants with severe tachypnea and distress are at risk • Tonsils may be covered with grayish-white
of aspiration with oral feedings. Maintenance IV pseudomembrane in cases of diphtheria and Epstein–
fluids are indicated during acute phase to maintain Barr virus infection. Draining cervical lymph nodes
hydration. may be enlarged and tender.
232
mebooksfree.com
Respiratory system Chapter | 14 |
j A narrow-spectrum cephalosporin (cephalexin or

Streptococcal cefadroxil) can also be used
Viral pharyngitis pharyngitis j For patients allergic to penicillin
• Gradual onset • Rapid onset – Erythromycin, Azithromycin, and clindamycin
• Rhinorrhea, cough, and • Prominent sore are used
diarrhea throat and fever in Complications
• Self-limiting and recovery the absence of cough
• Ear infections
within 5–7 days • Headache,
j Conjunctivitis, abdominal pain
• Peritonsillar, Retropharyngeal and Para-pharyngeal
abscess
coryza, hoarseness, and vomiting are
and cough common. • Non suppurative complications: Acute rheumatic
j Adenovirus • Pharynx—red, fever, acute post-infectious glomerulonephritis.
pharyngitis— tonsils enlarged, These complications can be prevented by timely
Concurrent covered with a administration of antibiotics
conjunctivitis yellow, blood-tinged
j Coxsackievirus exudate.
pharyngitis— • Petechiae or
Herpangina, Acute “doughnut” lesions 14.3 Acute
lymphonodular on the soft palate
pharyngitis and posterior
laryngotracheobronchitis (CROUP)
j HSV—High fever and pharynx
Gingivostomatitis • Anterior cervical • Croup is the most common cause of stridor
j EBV pharyngitis— lymph nodes— in children. Commonly seen in the age group
Prominent tonsillar enlarged and tender of 3 months to 5 years with peak at around
enlargement with • Scarlet fever— 2 years.
exudate, cervical Circumoral pallor, • Croup is characterized by infection of glottis and
lymphadenitis, strawberry tongue, subglottic region
hepatosplenomegaly, finely papular • Cases commonly occur during winter months, but
rash, and generalized rash that feels like sporadic cases occur throughout the year
fatigue sandpaper
Etiology
Diagnosis
• Parainfluenza viruses types 1, 2 and 3 (upto75%
cases)
• Complete blood count • Influenza A and B
• Throat swab culture—Gold standard • Adenovirus
• Rapid test to detect GABHS antigen—less sensitive • Respiratory syncytial virus
Management • Measles
• It is clinically difficult to differentiate between viral Pathogenesis
from bacterial etiologies. However, presence of
marked systemic involvement in the form of fever, • Viral pathogens enter epithelium of nasopharynx
toxicity, pus pointing on tonsils along with enlarged and spread locally to involve larynx and trachea.
tender cervical nodes and absence of nasal discharge Respiratory epithelial damage causes mucous
suggests bacterial pharyngitis. production, ciliary dysfunction and edema of
• Doubtful cases are often treated with antibiotics in subglottic region. As subglottic area is narrowest
order to prevent acute rheumatic fever. portion of airway in infants, any inflammation can
• Viral pharyngitis— greatly compromise the airway.
j Symptomatic therapy Clinical features
j An oral antipyretic/analgesic agent • Illness starts with subacute onset of fever, cough,
j Gargling with warm salt water cold and sore throat. Within 2–3 days of onset of
j Anesthetic sprays and lozenges symptoms, the characteristic “Barking” cough,
• Streptococcal pharyngitis hoarseness, and inspiratory stridor develops. These
j Penicillin V for 10 days: 250 mg/dose for children symptoms are aggravated with crying and agitation.
<27 kg and 500 mg/dose for others Occasionally wheezing can be heard when lower
j Oral amoxicillin: 30–50 mg/kg/day, maximum airway is involved. Symptoms are worse during
1 g, given orally for 10 days nights.
j A single intramuscular dose of benzathine penicillin • Severe cases present with tachypnea, suprasternal and
(600,000 U for children <27 kg; 1.2 million U for intercostal retractions, continuous stridor, hypoxia,
bigger children and adults) is equally efficacious cyanosis, altered sensorium and hypotonia.
233
mebooksfree.com

• Most cases have an uncomplicated course and
complete recovery with symptomatic treatment alone
• Less than 15 % have complications due to extension
of disease process
j Middle ear infection
j Bacterial tracheitis
j Pneumonia
• Most deaths are due to laryngeal obstruction and
complications of tracheostomy
14.4 Epiglottitis (Supra-glottitis)
Figure 14.2 Steeple sign in P A view X-ray of neck. • Acute life threatening airway obstruction due
to Inflammation and edema of epiglottis and
hypopharynx. Characterized by an acute rapidly
progressive and potentially fulminating course.
Diagnosis Complete obstruction of the airway and death can
• Diagnosis is often made solely on clinical grounds result if not identified and treated early. Commonly
• X-ray neck (PA view)—Subglottic narrowing or seen in children between 2 and 6 years. With routine
“steeple sign” (Fig. 14.2)—seen as tapering column Hib vaccination in National immunization schedule,
in upper trachea. Steeple sign may be absent in this condition is rarely seen in India these days.
patients and Xray findings do not indicate severity of Etiology
airway obstruction. • In the prevaccine era —H. influenza type b (Incidence
• Laboratory tests are of limited value reduced by 80%–90% following introduction of Hib
DDs vaccine)
• Epiglottitis • Streptococcus pyogenes
• Bacterial tracheitis • Streptococcus pneumoniae
• Foreign body aspiration • Staphylococcus aureus
• Angioedema Clinical features
• Retropharyngeal abscess • Patients present with high fever, sore throat, dyspnea,
• Laryngeal diphtheria and rapidly progressing respiratory obstruction. The
• Angioedema severity of respiratory distress may be variable at
Management presentation. Patients often appear toxic with labored
• Child should be hospitalized during acute stages. breathing along with marked suprasternal and
Child should be encouraged to stay in a position subcostal retractions of chest.
comfortable to them. • Drooling of saliva due to difficulty in swallowing is a
• Hydration should be maintained as fever and characteristic feature.
tachypnea leads to increased fluid loss • Child often hyperextends the neck to maintain the
• Humidified oxygen for hypoxic patients airway. Child may assume the tripod position—
• Nebulized racemic epinephrine—0.25–0.5 mL sitting upright and leaning forward with the chin up
of 2.25% racemic epinephrine in 3 mL of normal and mouth open.
saline • Progressive obstruction can cause severe hypoxia,
• Corticosteroids are beneficial- Dexamethasone restlessness, cyanosis and coma. Stridor is often a
a single dose of 0.6 mg/kg—IM/Oral is commonly late finding which suggests near complete airway
used obstruction.
• Nebulized budesonide is also equally effective Diagnosis
• No role for antibiotics • Diagnosis requires direct visual confirmation of
• In severe cases inflamed epiglottis. Direct laryngoscopy shows large,
j Airway management cherry red, swollen epiglottis (Fig. 14.3). There is
j Treatment of hypoxia variable involvement of supraglottic structures as well.
j Heliox mixture can be used in severe cases in Direct Laryngoscopy can be risky procedure in these
whom intubation is considered patients and should be performed in a controlled
234
mebooksfree.com
j Ceftriaxone, Cefotaxime, or Meropenem can also

be used
• Indications for Rifampin prophylaxis— 20 mg/kg
orally once a day for 4 days
j All household members
j Any contact < 48 months of age who is
incompletely immunized
j Contact < 12 months who has not received the
primary vaccination series
j An immunocompromised child in the
household
Complications
• Pulmonary edema
• Pneumonia
• Cervical lymphadenitis
• Otitis media
Figure 14.3 Swollen epiglottis on Direct laryngoscopy. • Meningitis
Source: A Practice of Anesthesia for Infants and Children,
2009.
• Septic arthritis
environment, ideally in an operating theatre or

intensive care unit where facility for emergency 14.5 Pneumonia
intubation is in place.
• Lateral X- ray of neck reveals the swollen epiglottis, • Defined as an inflammatory process involving lung
the characteristic “thumb sign”. Proper positioning parenchyma.
including hyperextension of neck is essential to
• Caused by a number of viruses and bacteria and no
capture this characteristic sign. causative pathogen is identified in about 50% of
• Cultures of blood, epiglottic surface should be cases.
collected after airway is stabilized
• The term ‘Pneumonitis’ is used for non-infective
DDs etiology
• Retropharyngeal abscess • Viruses are the most common cause in younger
• Peri-tonsillar abscess children, while bacteria are commoner in older
• Angioedema children
• Accidental ingestion of very hot liquid/corrosive Classification
Management • Pneumonia is classified as
• All suspected cases should be immediately j Community acquired pneumonia—It is acquired
hospitalized in Intensive care units. Instruments outside the hospital environment in a previously
required for emergency nasotracheal intubation healthy immuno-competent person. The patient
should be kept in place. Otolaryngologists should be should not have been hospitalized within 14 days
involved as there could be a need for tracheostomy. prior to the onset of symptoms.
Anxiety-provoking interventions should be avoided j Nosocomial pneumonia— It is acquired
until the airway is secure. within hospital setting more than 48 h after
• Epiglottitis is a medical emergency and warrants hospitalization [hospital-acquired pneumonia
immediate artificial airway by nasotracheal (HAP)] or more than 48 to 72 h after endotracheal
intubation or tracheostomy. Short term ventilation for intubation [ventilator associated pneumonia
2–3 days is sufficient in most patients. (VAP)].
• Child should receive humidified oxygen to treat • Pneumonia is classified anatomically as
hypoxia and IV fluids to maintain hydration j Lobar pneumonia—Involvement of large portion
• Patients should be started on antibiotics at the of one lobe or entire lobe of lung
earliest and there is prompt response to therapy. j Broncho pneumonia—Bilateral diffuse, patchy
Antibiotics should be continued for at least consolidation of lung
7–10 days. j Interstitial pneumonia—Involvement of
j Ampicillin 100 mg/kg/day supporting connective tissue present between
j Chloramphenicol 50 mg/kg/day alveoli and capillaries
235
mebooksfree.com
Etiology • Viral infection interferes with the defense

0–3 months Gram-negative Enterobacteriaceae mechanism of lungs by disturbing the normal
Enterococci function of respiratory epithelium. This can lead
Chlamydia trachomatis to dysfunction of ciliary brush border clearing
Group B streptococci mechanism.
Hemophilus influenzae • Phagocytosis by alveolar macrophages gets inhibited
Streptococcus pneumoniae and thus leading to invasion of lung parenchyma by
Listeria monocytogenes bacteria and other organisms. Bacterial invasion cause
3 months to 5 Streptococcus pneumoniae pneumonic lesion
years Viruses • The invasion can also occur either from direct spread
Hemophilus influenzae from nasopharyngeal tract by respiratory droplet
Staphylococcus infection or through hematogenous dissemination
Mycoplasma pneumoniae within the lung parenchyma.
>5 years Streptococcus pneumoniae j Invasive or bacteremic pneumonia—the spread is
Mycoplasma pneumoniae ‘hematogenous’
Viruses j Non-bacteremic pneumonia—the spread is ‘direct’
Staphylococcus Clinical features
Staphylococcus pyogenes Symptoms
• Triad of fever, cough, rapid and difficult breathing
• Other features include lethargy, poor feeding,
Risk factors vomiting, irritability, and cyanosis
• Low birth weight • Localized chest, abdominal, or neck pain can be present
• Malnutrition Signs
• Vitamin A deficiency • Sick looking, toxic child
• Lack of breastfeeding • Tachypnea, Nasal flaring, Chest indrawing, or Chest
• Passive smoking retractions
• Large family size and overcrowding • Oxygen saturation may be decreased
• Family history of bronchitis • End inspiratory coarse crackles over the affected area
Predisposing features • Classical signs of consolidation are
j Dullness on percussion
Organism Predisposing factors j Decreased breath sounds
Staphylococcus Pyoderma, skin abscess, measles j Bronchial breathing over the affected area
Pneumocystis Human immunodeficiency WHO grading of pneumonia
jiroveci virus (HIV) Pneumonia • Fever less than 38.5°C
Gram-negative, Neutropenia • No feeding difficulties
Aspergillus • No dehydration, cough and
Pseudomonas, Cystic Fibrosis tachypnea
Staphylococcus Severe • High-grade fever more than 39°C
Gram-negative, Severe protein-energy pneumonia • Difficulty in feeding
Staphylococcus malnutrition (PEM) • Tachypnea, Grunting
• Respiratory distress with intercostal
Viral Preceding coryza, wheeze
retraction (ICR) or subcostal
Chlamydia Young afebrile infant with retraction (SCR)
conjunctivitis • Dehydration
Mycoplasma Multisystem involvement (rash, • Bronchial breath sounds on
anemia, hepatitis, encephalitis) auscultation with or without crackles
Bacterial Marked leukocytosis • SpO2 > 92% at room air
• Radiological opacity on CXR +/–
Streptococcus Acute otitis media
pneumoniae / Very severe • Inability to feed
Hemophilus pneumonia • Altered sensorium
influenzae • Intermittent apneic spells
• Cyanosis
Pathogenesis • Excessive diaphoresis, Acidemia
• Narrow pulse pressure
• Usually preceded by a respiratory viral infection
• SpO2 < 92% at room air
236
mebooksfree.com
• Serology—serology, urinary antigens, rapid antigen

detection test (RADT) and cold agglutinins for
mycoplasma
• Nasopharyngeal swab for swine flu (H1N1)
• Invasive procedures—Bronchoscopy, BAL and lung
aspiration, have high sensitivity and specificity
• Pulse oximetry—Monitoring the course of the disease
in hospitalized children
Treatment
• Mainstay of management are antibiotics and
supportive therapy
• Outpatient management
j All nonsevere pneumonias more than 3 months
of age —First line oral antibiotics should be given
for minimum period of 5 days and second line for
7 days
Age First line Second line

3 months Amoxicillin Coamoxiclav/Cefuroxime/
to 5 years Chloramphenicol
> 5 years Amoxicillin Macrolides/Coamoxiclav/
Cefuroxime
• Inpatient management
j Indications for hospitalization include—Infants,
Severe cases (Hypoxemia, signs of respiratory
distress, impending respiratory failure), poor
feeding, inadequate response to oral antibiotics,
Immunocompromised, malnourished children etc.
j Management comprises of specific antimicrobial
along with supportive care of nutrition, hydration,
oxygen if needed, antipyretics (paracetamol) and
bronchodilators along with chest physiotherapy if
required.
j The duration for IV antibiotics should be for
5–7 days in uncomplicated cases, however, switch
Figure 14.4 (A) Bronchopneumonia. (B) Lobar pneumonia. over to oral antibiotics may be considered if
accepted orally.
j In case of methicillin-sensitive S. aureus
(MSSA), the duration should be for 2 weeks and
Diagnosis Methicillin-resistant S. aureus (MRSA) should be
• Complete hemogram treated for 4–6 weeks.
• Acute phase reactants like CRP and ESR j Swine flu is treated with Oseltamivir.
• Chest Xray
j Staphylococcal pneumonia—Pneumatoceles Age First line Second line
j Streptococcal pneumonia—Interstitial pneumonia
<3 months Cefotaxime/Ceftriaxone ±
j Atypical pneumonia—Hazy or fluffy exudates from
Aminoglycosides
hilar regions
j Pneumonia due to Gram negative organisms— 3 months Coamoxiclav or Ceftriaxone/
Unilateral/bilateral consolidation to 5 years Ampicillin + Cefotaxime
j Viral pneumonia—perihilar and peribronchial Chloramphenicol
infiltrates > 5 years Ampicillin/ Ceftriaxone/
j Bronchopneumonia (Figure 14.4A) Penicillin G Coamox- Cefotaxime and
j Lobar pneumonia (Fig. 14.4 B) iclav/Macrolide Macrolides
• Sputum culture (Only in suspected tuberculosis) or (if mycoplasma
blood culture suspected)
237
mebooksfree.com
j Amoxicillin or ampicillin
Age First line Second line j Ceftriaxone or cefotaxime
Suspected Cefuroxime or Ceftriaxone/
Staph Coamoxiclav or Cefotaxime and
IV 3rd generation Vancomycin/
14.5.2 Staphylococcal pneumonia
Cephalosporins + Teicoplanin/ • Most common age group—infant and childhood
Cloxacillin Linezolid • Predisposing factors—malnutrition, macrophage
dysfunction, DM
14.5.1 Pneumococcal pneumonia Pathology
• Diffuse inflammation
• Most common in children 3 weeks to 4 years • Suppurated lesions
of age • Bronchoalveolar destruction
• Mode of transmission—droplet infection • Multiple microabcess
• More common during winter • Several pneumatoceles
• Predisposing factors—overcrowding, diminished host • Abscess may erode into neighboring tissues causing—
resistance empyema, pericarditis
Pathology Clinical features
• Multiplication of bacteria in alveoli • Usually follows URI/pyoderma
• Inflammatory exudates • Fever, anorexia, irritability, listless
• Scattered areas of consolidation coalesce around • Fast breathing, retraction
bronchi to form lobar/lobular consolidation • Rapid worsening with cyanosis
• Stages • Involvement of other systems due to disseminated
j Congestion infection can be noted
Red hepatization
Diagnosis
j
Gray hepatization
• Evidence of staphylococcal infection elsewhere
j
Resolution
• Evidence of complications such as pyopneumothorax
j
Clinical features or pericarditis

• Incubation period—(1–3) days • CXR—Pneumatoceles (Fig. 14.5)
• High grade fever, chills, cough, headache • Positive blood culture
• Thick rusty red sputum in older children Treatment
• Pleural pain—May be perceived as referred shoulder • Oxygen
or abdominal pain
• IV fluids
• Meningismus—may be present in apical pneumonia • Antibiotics
• Severe cases present with fast breathing, grunting, j Penicillin G
chest in-drawing, difficulty in feeding and cyanosis
j Erythromycin
j Auscultation may reveal, decreased air entry,
crepitations and bronchial breathing
• Percussion note is impaired over areas of
consolidation
• Bronchophony and whispering pectoriloquy may be
present
Diagnosis
• History
• Physical examination
• CBC—leucocytosis with neutrophilic predominance
• CXR—lobar consolidation
• Blood culture—positive in 5%–15%
Treatment
• Oxygen—if cyanosis or respiratory distress
• IV fluids to maintain hydration
• Antibiotics
j Penicillin G 50,000 units/kg/day IM/IV for
5–7 days
j Procaine penicillin 600,000 units IM
j Penicillin V orally Figure 14.5 Right sided Pneumatocele.
238
mebooksfree.com
j Cloxacillin (100 mg/kg/day in 4 divided doses) • Delay in recognition and removal leads to chronic
j Cephalosporin complications
j If MRSA—vancomycin/linezolid/teicoplanin Epidemiology
• Empyema —Intercostal drainage
• Duration of treatment—At least 2 weeks for • Most commonly seen among preschoolers—75%–90%
pneumonia and 4–6 weeks for empyema j < 1year - 10%–15%
Complications j 1–2 years - 40%–50%
• Empyema j 2–3 years - 15%–25%
• Pyopneumothorax
• Pericarditis j 3 years - 15%–20%
• Metastatic abscess
• Pleural thickening—may require decortication • Boys are more affected than girls—2:1
• More incidence noticed during vacation period
• Usual foreign bodies
14.5.3 Atypical pneumonia j Food items are the commonest aspirated foreign
bodies—(65%–85%)
• Most common organisms
j Mycoplasma – Peanut is the most commonly encountered FB
j Chlamydia – Others—candies, gums, chocolate
j Pneumocystis jiroveci—in immunocompromised – Organic FB cause intense inflammation and
children worsen obstruction
Small toys
• Mode of transmission—droplet infection j
Marbles
• Uncommon below 4 years of age j
j Coins
Clinical features j Latex balloons
• Incubation period—12– 14 days
Location
• Insidious onset
• Fever, cough, sore throat, malaise, headache • Usual location of foreign body—Right mainstem
• Mild pharyngeal congestion (30%–40% cases) bronchus followed by left main
• Cervical lymphadenopathy bronchus, Right and left lobar bronchus, trachea, and
• Extrapulmonary manifestation—hemolytic anemia larynx.
• On auscultation—few scattered crepitations Pathogenesis
Diagnosis • Certain anatomic and cognitive constrains predispose
• CBC—Normal for aspiration
• In acute stage ELISA IgM is positive j Oral phase—tendency to put everything in the
• After 1week IgG antibodies can be demonstrated by mouth
complement fixation test j Poor mastication
• CXR—hazy, fluffy infiltrates; enlarged hilar lymph j Inadequate control of deglutination
node; pleural effusion can be present • Crying/laughing while eating
Treatment • Certain parental behavior like spanking/thumping
while feeding, feeding a crying child
• Macrolide antibiotics
j Erythromycin • Loss of coordination during swallowing
j Azithromycin • 90% of FBs are coughed out during choking due to
j Clarithromycin strong cough reflex and only 10% gets lodged in the
j Roxithromycin airways
j Tertracycline for older children Pathophysiology
• Duration of treatment: 7–10 days • Near total obstruction at larynx and trachea causes
immediate asphyxia and death
• Once it crosses the carina FB may subsequently
change in position and migrate distally
14.6 Foreign body aspiration • It can cause obstruction and cause inflammation,
edema, infiltration, ulceration and granulation
• Foreign body (FB) aspiration is one of the very formation leading to airway obstruction
common pediatric emergency encountered in infants • The possibility of complications increases after
and toddlers 24–48 h
• It is completely treatable and to a much extent • Possible complications are
preventable condition j Atelectasis
239
mebooksfree.com
j Emphysema • Fluoroscopy
j Pneumonia j More sensitive than CXR
j Abscess j Useful when plain radiograph is inconclusive
j Bronchiectasis j Shows phasic mediastinal shift during inspiration
Clinical presentation indicating the site of FB
• Child with FB aspiration can present with any of the 3 • CT scan
phase of symptom j CT with contrast is more useful in suspected
• Phase I: Choking chronic FB
j Immediately after aspiration, child develops • Ventilation perfusion scan
violent cough, acute respiratory distress, stridor • Bronchoscopy—definitive diagnostic and
and/or wheeze therapeutic
• Phase II: Asymptomatic Treatment
j FB gets lodged and symptoms subside • Emergency management
j It is during this stage FB is forgotten or neglected j If FB is visualized, extract carefully
j It can last from hours to weeks j Avoid blind finger sweeps
• Phase III: Complications • In a conscious child, coughing should be
j Patient presents with secondary complications due encouraged
to airway obstruction or infection • In Infants—5 back blow followed by 5 chest
j Recurrent respiratory symptoms—Recurrent cough, thrusts
wheeze, pneumonia • If child > 1 year—Heimlich maneuver—(6–10)
j Chronic respiratory symptoms—Hemoptysis, abdominal thrusts
nonresolving pneumonia, bronchiectasis, lung • These measures should not be performed in a child
abscess who is breathing, able to speak or crying
Investigation • If the above measures fail
• CXR j Urgent cricothyrotomy
j Radio-opaque FB are seen only in 10%–25 % of j Tracheostomy
patients j Endotracheal intubation with smaller size tube
j Expiratory films along with lateral decubitus • Rigid bronchoscopic removal
view are more useful in detecting air trapping • Thoracotomy/Lobectomy—if bronchoscopic removal
(Fig. 14.6) is not feasible
j Lobar emphysema, bronchiectasis, and pneumonia • Antibiotics for secondary infection
can be present • Steroid for inflammation
• Treat secondary complications
14.7 Lung abscess
Definition
• Lung infection that destroys the lung parenchyma,
resulting in cavitation and central necrosis, can result
in localized areas composed of thick-walled purulent
material, called lung abscesses.
• Primary—occur in previously healthy patients, mostly
found on right side
• Secondary—occur in patients with underlying
or predisposing conditions, mostly found on left
side
Predisposing conditions
• Aspiration
• Pneumonia
• Cystic fibrosis
• Gastroesophageal reflux
Figure 14.6 Obstructive emphysema on left side with • Tracheoesophageal fistula
mediastinal shift to right side. • Immunodeficiencies
240
mebooksfree.com
Common organisms
• Aerobic
j Streptococcus
j S. aureus
j Escherichia coli
j Klebsiella pneumoniae
j Pseudomonas aeruginosa
j Mycoplasma pneumoniae
• Anaerobic
j Bacteroides spp.
j Fusobacterium spp.
j Peptostreptococcus spp.
• Fungal—in immunocompromised patients
Pathogenesis
Figure 14.7 Lung abscess.
Treatment
• Antibiotics
j Start with broad spectrum penicillinase resistant
agent with anaerobic coverage
j Switch once culture and sensitivity is obtained
j Duration—total 4–6 weeks
j Initially IV 2–3 weeks, if improving
j Oral for remaining course completion
• If not responding to antibiotics
j CT guided percutaneous drainage
Thoracoscopic drainage
Clinical features
j
Surgical lobectomy ± decortication
• Fever
j
Radiological resolution takes 1–3 months

• Anorexia
j
• Lethargy
• Cough with foul smelling expectoration
• Tachypnea 14.8 Bronchiectasis
• Dypnea
• Chest pain Definition
• Hemoptysis • Abnormal irreversible dilatation and distortion of
• On examination bronchial tree
j Decreased breath sounds • Chronic suppurative lung disease
Dullness on percussion
Etiology
j
Coarse crepitations
• Cystic fibrosis (most common)
j
Whispering pectoriloquy
• Primary ciliary dyskinesia
j
Diagnosis • Foreign-body aspiration

• CBC—Elevated counts with neutrophilic • Immune deficiency syndromes
predominance • Infection—pertussis, measles, and tuberculosis
• ESR—Elevated • Congenital syndromes
• Sputum—gram stain with culture and sensitivity j Williams-Campbell syndrome—an absence of
• CXR—Parenchymal inflammation with a thick walled annular bronchial cartilage
cavity containing an air–fluid level (Fig. 14.7) j Marnier-Kuhn syndrome—congenital
• CT scan—better information of location and size tracheobronchomegaly in which there is a
• CT guidance percutaneous or transtracheal aspiration connective tissue disorder
of abscess and microbiological evaluation j Right middle lobe syndrome—chronic extrinsic
• Bronchoscopy and bronchoalveolar lavage for compression of right middle lobe bronchus by
analysis hilar lymph nodes
241
mebooksfree.com
j Yellow nail syndrome—pleural effusion, Physical examination

lymphedema, discolored nails • Coarse leathery Crackles localized to the affected
Pathogenesis area
• Wheezing
• Pan digital clubbing may also occur
• In severe cases—dyspnea and hypoxemia
• Pulmonary function test—an obstructive, restrictive,
or mixed pattern. Impaired diffusion capacity in late
stages
Diagnosis
• CXR
j Increase in size and loss of bronchovascular
markings, crowding of bronchi, and loss of lung
volume
j In severe forms—cystic spaces with air–fluid levels,
honeycombing and compensatory overinflation of
unaffected lung
• HRCT (Gold standard)
j Location and the extent of segmental involvement
can be made out
j Cylindrical—“tram lines,” “signet ring appearance”
Pathological forms (Fig. 14.8) j Varicose—“beaded contour”
• Cylindrical bronchiectasis—bronchial outlines j Cystic—“strings and clusters”
are regular, but diffuse dilation of the bronchial • Bronchoscopy—to identify anatomical abnormality
tree • Conditions that can be associated with bronchiectasis
• Varicose bronchiectasis—dilation is greater with should be ruled out—e.g., sweat chloride test,
local constrictions causing irregularity of outline immunologic work- up, tuberculin test, sputum culture
resembling that of varicose veins and sensitivity
• Saccular/Cystic bronchiectasis—bronchial dilation Management
progresses and results in ballooning of bronchi (most • Airway clearance
severe) j Effective coughing at regular interval
Clinical features j Postural drainage
• Cough j Pulmonary physiotherapy
• Expectoration—copious purulent sputum • Antibiotics
• Hemoptysis j Oral antibiotics—amoxicillin with clavulanic
• Fever with recurrent LRTI acid
• Anorexia and poor weight gain j In severe cases—broad spectrum IV antibiotics or
according to culture sensitivity
j Nebulized antibiotics
• Nebulization
j Bronchodilators/Corticosteroids
• Segmental/Lobar resection if not responding to
medical management
• Lung transplantation
Prevention
• Early and effective management during
exacerbation
• Immunization—influenza, measles, pertussis,
pneumococci
Prognosis
• Early identification, prompt treatment during
exacerbations and preventive measures will decrease
the episode of recurrent exacerbation and improve the
Figure 14.8 Morphological types of Bronchiectasis. quality of life
242
mebooksfree.com
• Newborn screening test

14.9 Cystic fibrosis j Combination of immunoreactive trypsinogen and
limited DNA testing on blood spots
• Autosomal recessive disorder j Positive screens are followed by a confirmatory
• Most common life limiting inherited multisystem sweat analysis
disorder of exocrine glands • Sweat Chloride Test
Uses Pilocarpine iontophoresis
Genetics
j
Testing difficult in the 1st 2 weeks of life due to

• Dysfunction of CFTR (cystic fibrosis transmembrane
j
low sweat rate

conductance regulator protein) gene located at long
More than 60 mEq/L of chloride in sweat is
arm of chromosome 7
j
diagnostic
• More than 1400 mutations
• Commonest mutation delta F 508 • DNA Testing— CFTR mutations
• Frequency of mutation in Indian children • Nasal potential difference measurement—
Increased
25%–30%
• Exocrine pancreatic dysfunction—quantification of
Pathology elastase-1 activity in stool sample by an enzyme-
• CFTR is expressed in epithelial cells of airways, linked immunosorbent assay
the gastrointestinal tract (including the pancreas
Management
and biliary system), the sweat glands, and the
genitourinary system. • Respiratory management
Airway clearance
• Failure of chloride conductance by epithelial cells
j
– Pulmonary physiotherapy
leading on to paucity of water and elevated salt
– Nebulization
content in mucous secretions
– Endoscopy and lavage
• Dehydration of secretions that become too viscid and
Antibiotics
elastic
j
Antiinflammatory agents
• Failure to clear mucous secretions leading on to
j
airway obstruction • Nutritional management

Increased calorie intake
• Similar events in the pancreatic, biliary ducts and in
j
Fat soluble vitamin supplementation—A, D, E, K

the vas deferens, etc.
j
Pancreatic enzyme replacement—

• Desiccation of proteinaceous secretions and
j
– Lipase 1000–2000 IU/kg divided for each feed

obstruction
• Failure to clear inhaled bacteria promptly leading to Complications
persistent colonization and inflammation Respiratory Gastrointes- Others
Clinical feature • Nasal polyps tinal • Infertility
• Common clinical presentation according to age • Sinusitis • Meconium • Delayed
• Neonates present with delayed passage of meconium • Bronchiecta- ileus, meco- puberty
and rarely meconium ileus sis, bronchi- nium plug, • Edema-hy-
• Infants present with recurrent bronchiolitis, tis, bron- Meconium poproteine-
Hyponatremic hypochloremic metabolic alkalosis chiolitis, peritonitis mia
and rarely rectal prolapse pneumonia (neonate) • Dehydra-
• During Childhood • Reactive air- • Rectal tion–heat
j Sinusitis, Recurrent LRTI with Pseudomonas way disease prolapse exhaustion
• Allergic • Intussuscep- • Hypertroph-
species
bronchopul- tion ic osteoar-
j Bronchiectasis
monary • Pancreatitis thropathy
j Chronic lung disease
aspergillosis • Cholelithi- arthritis
j Chronic diarrhea, Steatorrhea asis • Amyloidosis
j Intussusception, Biliary fibrosis • Growth fail-
• During Adolescence ure (malab-
j Delayed puberty, Azoospermia sorption)
j Diabetes mellitus
j Allergic bronchopulmonary aspergillosis
j Distal intestinal obstruction syndrome
j Biliary cirrhosis 14.10 Empyema
Diagnosis
• Heterozygote and prenatal testing—in individuals • Empyema is an accumulation of pus in the pleural
with positive family history space
243
mebooksfree.com
• It is most often associated with bacterial

pneumonia
• More common in infants and preschool children
Causes
• Staphylococcus aureus (most common)
• Streptococcus pneumoniae
• Haemophilus influenzae
• Group A streptococcus
• Gram-negative organisms
• Tuberculosis, Fungi, Malignancy
• Rupture of a lung abscess into the pleural space
• Mediastinitis or the extension of intraabdominal
abscesses.
Pathology
• 3 stages
j Exudative stage—fibrinous exudate forms on the
pleural surfaces
j Fibrinopurulent stage—fibrinous septa form, Figure 14.9 Empyema.
causing loculation of the fluid and thickening of
the parietal pleura • Pleural tap—purulent material full of pus cells with
j Organizational stage—fibroblast proliferation pH is <7.20, elevated >100,000 neutrophils/µL, high
with pockets of loculated pus protein and low sugar.
Clinical features • Gram stain and culture of pleural fluid may show
• History of pneumonia and treated with antibiotics in causative agent.
recent past Complication
• Fever • Bronchopleural fistula
• Dyspnea • Pyopneumothorax
• Toxic appearance • Purulent pericarditis
• Chest pain • Pulmonary abscesses
• Decreased movement of respiration on affected side • Peritonitis
• Decreased air entry and vocal resonance • Osteomyelitis of the ribs
• Dull on percussion • Septic complications—meningitis, arthritis,
• Empyema necessitans – Extension of empyema from osteomyelitis
pleural space into the subcutaneous tissue of the chest Treatment
wall • Antibiotics—IV antibiotics (2–4) weeks
Diagnosis • Cloxacillin, Vancomycin, Linezolid and Clindamycin
• CBC—Leukocytosis with neutrophilic predominance are commonly used first line drugs
• ESR—Elevated • Inter costal drainage
• CXR—shows shift in mediastinum with obliteration • Thoracocentesis with fibrinolytic administration
of costophrenic angle and varying degree of • VATS—video assisted thoracocentesis
opacification (Fig. 14.9) • Open decortication
244
mebooksfree.com
Chapter | 15 |
Nephrology
• It is commonly seen in School age boys (>3 years)

15.1 Glomerulonephritis and extremely rare below that age. Sudden onset of
nephritis occurs 1–4 weeks following streptoccocal
Glomerulonephritis (GN) includes a group of immune infection. Their nephritogenicity of the organism
mediated diseases characterized by inflammation and is related to the M-protein serotype. Common
proliferation of glomerular tissue with damage to the glo- nephritogenic streptococcal strains are type M1, M4,
merular basement membrane, mesangium, or capillary M12, and M25 (following pharyngitis) and M2, M49,
endothelium. The pathology of GN can be limited to the M56, and M60 (following pyoderma)
kidney (primary) or part of a systemic disorder (second- Pathogenesis
ary). Depending on the onset and rate of progression, • Basic mechanism of pathogenesis in PSGN is due to
GN is clinically classified as acute, rapidly progressive or Molecular mimicry. Antibodies against streptococcal
chronic GN. antigens react with normal glomerular antigens
leading on to immune complex formation and
subsequent complement activation.
• Deposition of immune complexes formed either in
15.2 Acute glomerulonephritis/ the circulation or binding of antibodies to antigens
acute nephritic syndrome trapped in the glomerulus leads to activation of
complement pathway. Depression in the serum
Acute nephritis is characterized by rapid onset hematuria, complement (C3) provides a strong evidence of
proteinuria, associated with hypertension, edema and re- immune mediated renal injury.
nal insufficiency. Postinfectious GN is the most common • Release of leukocyte, macrophages, cytokines
cause of GN in children out of which approximately 80% further accentuates renal injury
cases have poststreptococcal etiology. IgA nephropathy is • Histopathological involvement does not always
the most common cause of acute nephritis in less than correlate with clinical severity
5 years (Table 15.1). Pathology (Fig. 15.1)
• Light microscopy
j Enlarged and ischemic glomeruli
15.3 Post streptococcal j Endothelial and diffuse mesangial cell proliferation
Neutrophilic infiltration in early stages
glomerulonephritis
j
j Crescents and interstitial inflammation seen in

severe cases
• Poststreptococcal glomerulonephritis (PSGN) • Electron microscopy—‘Electron dense’ deposits of IgG
presents with gross hematuria, edema, elevated and complement on sub-epithelial side of glomerular
blood pressure and renal insufficiency. PSGN is a basement membrane and in mesangium
postinfectious sequelae secondary to nephritis and • Immunofluorescence - Granular deposits of IgG and
pharyngitis caused by group A beta haemolytic complement along capillary wall (‘Lumpy–Bumpy’
streptococcus. deposits Fig. 15.2)
245
mebooksfree.com
Table 15.1 Cause of Acute Glomerulonephritis

(Acute GN)
1. Postinfectious
j Bacteria: Group A β-hemolytic Streptococci
(Most common), Staphylococci, Pneumococci,
Meningococci, Treponema pallidum, Salmonella
typhi, Leptospira
j Viruses: Hepatitis B and C, Cytomegalovirus,
Ebstein-Barr virus, Coxsackie virus, Varicella,
Rubella, Mumps
j Parasites: Plasmodium malariae, P. falciparum,
Toxoplasma, filariasis, Schistosoma mansoni
j Misc: Infective endocarditis, Infection of indwelling
catheters, shunts and prosthesis,
2. Noninfectious
j Primary renal diseases
– IgA nephropathy
– Mesangial proliferative glomerulonephritis
– Focal segmental glomerulosclerosis Figure 15.2 Bright green granular, bumpy pattern of sub-
– Alport’s syndrome epithelial immune deposits in PSGN. (Pic Courtesy: Dr. Srinivas
– Membranoproliferative glomerulonephritis BH, JIPMER, Puducherry)
j Systemic diseases
with edema, hypertension and oliguria depending on
– Vasculitis: Wegener’s granulomatosis,
the severity of renal involvement.
Microscopic polyangiitis, Henoch-Schönlein
purpura • Edema starts as Facial puffiness and can
– Connective tissue diseases: Lupus nephritis progress to Pedal edema, ascites and anasarca in
j Drugs severe cases. Gross hematuria, often described as
– Gold, Penicillamine ‘Cola colored urine’ lasts for few hours to few days.
Patients with severe hypertension and hypervolemia
are at risk of developing heart failure and
Clinical features encephalopathy. Patients with hypertension should
• PSGN is commonly seen in children aged 5–12 years be monitored for symptoms of encephalopathy such
with male preponderance. Affected children classically as blurred vision, headaches, altered mental status
present with acute onset nephritic syndrome and seizures. Nonspecific symptoms like malaise,
1–2 weeks following streptococcal pharyngitis or lethargy, abdominal/flank pain can occur.
3–6 weeks after a streptococcal skin infection. Acute • The acute phase usually resolves within 6–8 weeks in
nephritic syndrome occurring within 3–4 days most cases.
following respiratory or GI infection suggests IgA Laboratory findings
nephropathy or Alport syndrome. Patients present • Urine analysis reveals dysmorphic RBC cells,
RBC cast, polymorphonuclear leukocytes and
proteinuria
• Normochromic anemia (hemodilution), Low grade
Hemolysis, Raised ESR
• Increased blood urea and creatinine
• Electrolyte abnormality—Hyponatremia, Hyperkalemia,
Metabolic acidosis
• Low serum C3 level can be demonstrated in the acute
phase but usually normalizes by 5–6 weeks. Serum
CH50 is usually reduced but C4 levels are normal or
mildly depressed.
• Evidence of prior streptococcal infection required for
confirming diagnosis
j ASO titres (Sore throat) and Anti DNAase B titres
(Skin infection) increased
j Streptozyme test
Figure 15.1 Immune complex deposition in Nephritis j Throat swab for Beta hemolytic streptococcus
246
mebooksfree.com
Nephrology Chapter | 15 |
• X-ray chest—prominent broncho-vascular marking Prognosis

indicating hypervolemia, rarely, cardiomegaly and • Symptoms usually resolve within first two weeks of
pulmonary edema treatment. Long-term outcome is excellent. Complete
• Indications for Renal biopsy recovery in >95% children and recurrences are
j Acute Renal failure extremely rare. Less than 2% of affected children
j Nephrotic syndrome develop chronic kidney disease. Proteinuria and
j Renal function impaired severely beyond 10–14 days hypertension usually subside by 4–6 weeks but
j Normal complement levels microscopic hematuria can persist upto 1–2 years.
j Serum C3 remains low for more than 2 months Careful long-term follow-up for urine examination and
j Unresolving glomerulonephritis. measurement of blood pressure is essential
j Nephrotic range proteinuria. Prevention
Complications • Acute nephritic syndrome can occur even if
streptococcal infections were identified and
• Hypertension (60%) and Hypertensive emergency
(10% cases) treated early with antibiotics. Family members should
be screened and treated for streptococcal carriage.
• Convulsions
• Heart failure and Pulmonary edema
• Acute renal failure
• Dyselectrolemia: Hyperphosphatemia, Hypocalcemia 15.4 Rapidly progressive
Management (Crescentic) Glomerulonephritis
Treatment is mainly symptomatic. Patients with oliguria (RPGN)
and hypertension should be hospitalized. Strict bed rest is
not required in mild cases.
• RPGN includes several forms of acute GN
• Diet: characterized by rapid progression to end-stage renal
j Sodium and fluid restriction failure and presence of crescents in the majority of
j Protein and Potassium restriction till renal glomeruli in histopathology. Fortunately, RPGN is
insufficiency normalizes less common in children. RPGN is also known as
j Diet protein should be restricted until blood levels crescentic glomerulonephritis
of urea reduces and urine output increases Pathology
• Daily weight monitoring
• Presence of extensive crescents on renal biopsy
j Fluid intake is to be reduced if weight gain is evident. is the histological hallmark of RPGN. Crescent
• Fluid restriction formation occurs by two or more layers of segmental
j Fluid intake should be restricted to insensible to circumferential proliferation of parietal epithelial
losses and 24 h urine output. Hypervolemia can cells in Bowman’s space leading to its obliteration
worsen hypertension and precipitate pulmonary (Fig. 15.3). Typically more than 50% glomeruli
edema secondary to left ventricular failure
• Diuretics
j Not indicated in mild edema
j Furosemide (2–4 mg/kg) in presence of
pulmonary edema
• Hypertension
j Fluid and salt restriction
j Antihypertensives include beta blockers, ACE
inhibitors and nifedipine
j Malignant hypertension would require prompt
treatment with IV nitroprusside or labetalol
• Left ventricular failure
j Hypertension should be controlled
j Intravenous furosemide to induce diuresis
j Urgent dialysis if no immediate diuresis after IV
furosemide administration
• Dialysis required in severe renal failure, prolonged
oligoanuria, fluid overload and severe electrolyte
abnormalities Figure 15.3 Collapsed glomerular tuft and crescent
• Systemic Antibiotics: Penicillin course for 10 days to formation in RPGN. (Pic Courtesy: Dr. Srinivas BH, JIPMER,
limit the spread of nephritogenic strains. Puducherry)
247
mebooksfree.com
Table 15.2 Classification of Rapidly Progressive • (p-ANCA) in renal limited vasculitis, microscopic

Glomerulonephritis polyangiitis and drug-induced pauci-immune GN.
• Renal biopsy with light, immunofluorescence,
Type I: Anti–GBM antibody disease (Uncommon) and electron microscopy is needed in all since
• Goodpasture syndrome occasionally diffuse proliferative GN or thrombotic
• Postrenal transplant in Alport syndrome microangiopathy (TMA) may have similar clinical
Type II: Immune complex mediated (50%–70% cases) presentation.
• Ig A nephropathy
Treatment
• HSP nephritis
• PSGN
• Early diagnosis and treatment is crucial as there
is progression to end stage renal disease (ESRD)
• Lupus nephritis
associated with poor outcome.
Type III: Pauci-immune (usually ANCA positive)
(15%–30% cases) • High-dose corticosteroids and cyclophosphamide
• Microscopic polyangiitis can prevent ESRD in SLE nephritis, HSP nephritis,
• Wegener’s granulomatosis Wegener granulomatosis, and IgA nephropathy
if started early when histology shows numerous
cellular crescents. IV methylprednisolone
have crescents. These crescents rapidly evolve into (15–20 mg/kg, maximum 1 g/day) for 3–6 days
fibrocellular and fibrous bands late in the course. is the usual initial therapy, followed by oral
• It is classified into three types based on the prednisolone (1.5 mg/kg daily) for 4–6 weeks,
mechanisms of renal injury (Table 15.2). with tapering to 0.5 mg/kg daily by 3 months,
• Renal immunofluorescence along with electron and alternate day dosing for 12 months.
microscopy pattern of immune deposits can IV cyclophosphamide (500–750 mg/m2) is
identify the underlying glomerulopathy causing administered monthly for 6 doses.
RPGN. • Pauci-immune and anti-GBM disease respond to
• Immunofluorescence and electron microscopy plasmapheresis for 10–14 days, but this can also
shows minimal or no findings. This is a characteristic be tried in refractory lupus nephritis and HSP
feature of pauciimmune GN (Wegener disease and nephritis. Azathioprine (2 mg/ kg) and alternate day
microscopic polyangiitis) prednisolone are used for long-term maintenance
Clinical Features of immunosuppression in patients with ANCA
• RPGN typically starts as an acute GN (hematuria, associated RPGN.
edema, hypertension, oligoanuria and azotemia) • Other agents tried with limited success are
that rapidly progresses into end-stage renal mycophenolate mofetil, cyclosporine, anti-CD20
disease. Extrarenal manifestations like pulmonary, antibodies and IV immunoglobulin.
musculoskeletal, skin and neurological Prognosis
manifestations can help in finding the underlying • Progression to ESRD often occurs despite aggressive
cause of RPGN. immunosuppressive therapy. Though RPGN
• Renal biopsy is indicated in all cases of acute GN secondary to post-infectious GN can recover
that does not resolve within 2–3 weeks. Some cases spontaneously, the outcomes of other etiologies are
of RPGN have no identifiable underlying cause on uniformly poor. Etiology other than PSGN, presence
serologic testing, or histologic examination and are of fibrous crescents in renal histology, severity of renal
termed as ‘Idiopathic RPGN’. failure, late or poor response to therapy are factors
Diagnosis predicting poor prognosis in RPGN.
• Investigations include blood counts, urinalysis
(hematuria, proteinuria, red cell casts), blood levels
of urea, creatinine and C3 (low in PSGN, lupus and 15.5 Henoch-schonlein purpura
MPGN).
(HSP) nephritis
• Serology includes antistreptolysin-O in preceding
streptococcal infection; and antinuclear and anti-
dsDNA autoantibodies in lupus. • HSP is the most common small vessel vasculitis in
• Antinuclear cytoplasmic antibodies with children. Clinical triad of nonthrombocytopenic
specificity for proteinase 3 produce cytoplasmic palpable purpura, transient arthritis and abdominal
staining on immunofluorescence (c-ANCA), e.g., symptoms are seen. Symptoms usually follow an
Wegener’s granulomatosis. Myeloperoxidase upper respiratory infection. Renal involvement occurs
specific ANCA produces perinuclear staining on in approximately 50% of patients. HSP nephritis is
immunofluorescence mediated by IgA immune complexes.
248
mebooksfree.com
Table 15.3 Criteria for HSP in children
Palpable purpura in presence of at least one of the

following 4 features
• Diffuse abdominal pain
• Any biopsy showing IgA deposition
• Arthritis or arthralgia
• Renal involvement (hematuria /proteinuria)
Pathology
• Deposition of polymeric IgA and IgA immune
complexes in glomeruli. This is similar to the IgA
deposits in other organs like in systemic small
vessels, especially in the skin and intestine. The
histopathology cannot be differentiated (Fig. 15.1)
from IgA nephropathy. There is mesangial
proliferation with characteristic IgA deposits in
mesangium and in severe cases, crescent formation
may be seen (Table 15.3).
Clinical features
• Henoch–Schönlein purpura can occur at any age but
is most common in childhood.
• Symptoms begin with a purpuric rash over
extensor aspect of lower extremities and buttocks
(Fig. 15.4). Rash start as pink macules or wheals
and develops into petechiae, raised purpura or larger
ecchymoses. Arthritis and arthralgias can occur upto
75% of cases. Neurologic manifestations include
hypertension, intra cranial hemorrage and seizures.
• Renal involvement can range from isolated
hematuria, hypertension, nephritic to frank
nephrotic syndrome. Acute Glomerulonephritis
is present in one third of patients. Renal
involvement uncommon <6 years. The severity Figure 15.4 Palpable purpuric rash in both lower
of the extrarenal manifestations does not correlate extremities seen in HSP. Source: Paediatrics and Child Health, 2011
with nephritis.
• Gastrointestinal symptoms occurs in 7–10 days.
Usual symptoms are periumbilical, colicky,
intermittent abdominal pain, Vomiting, diarrhea Treatment
and paralytic ileus. Less common are pulmonary • Spontaneous resolution often occurs in mild
hemorrhage, orchitis and carditis. cases of HSP nephritis. Drug therapy is warrented
• Clinical features of HSP are self-limiting where in moderate to severe nephritis which is are at
extra-renal symptoms resolve rapidly without high risk for progressing into chronic kidney
any complication. Long-term prognosis is mainly disease. The usual recommended therapy is of
dependent on the severity of renal involvement. Prednisolone (1–1.5 mg/kg/day) for 2–3 weeks
or Azathioprine, cyclophosphamide, and
Laboratory investigation
mycophenolate mofetil.
• Leukocytosis, thrombocytosis and mild anemia • Supportive with maintenance of hydration and pain
• Elevated ESR and C-reactive protein relief
• Increased total serum IgA levels
• Serum protein Prognosis
• Microscopic hematuria and proteinuria • Usually self-limiting in 4 weeks with no permanent
• Ultrasound abdomen sequlae. Recurrence occurs in 60% patients within
• Skin biopsy—leukocytoclastic vasculitis 4–6 months of diagnosis. Children >6 years can
• Renal biopsy—mesangial proliferation with IgA develop RPGN. Approximately 1–5% can progress to
deposition end stage renal disease.
249
mebooksfree.com
• Predisposing factors –
15.6 Hemolytic uraemic j Neuraminidase producing Strep pneumoniae
syndrome (HUS) j Cyclosporin
j Mitomycin
• Common cause of acute kidney injury in young Pathology
children • Renal microvascular injury with endothelial cell
• Classical triad of features damage is characteristic primary injury
j Microangiopathic hemolytic anemia • E. coli produces shiga like toxin which causes direct
j Thrombocytopenia endothelial injury and platelet aggregation
j Renal insufficiency • Neuraminidase cleaves sialic acid on membranes of
• HUS shares common features with thrombotic endothelial cells, red cells, and platelets to trigger the
thrombocytopenic purpura (TTP) microvascular angiopathy
• Classified into two types • In inherited HUS, ADAMTS13 impairs cleavage of
j D+ HUS or typical HUS von Willebrand factor
j D− HUS or atypical HUS • Early glomerular changes:
Etiology of HUS j Accumulation of fibrillar material between
endothelial cells and its basement membrane,
1. Typical HUS causing narrowing and thickening of capillaries.
Infectious causes: j Platelet-fibrin thrombi in glomerular capillaries
j Escherichia coli O157:H7 and afferent arterioles
j Shigella dysenteriae 1 j Fibrinoid necrosis in the wall of small arteries,
j Citrobacter freundii leading to renal cortical necrosis from vascular
2. Atypical HUS occlusion.
Infectious causes: • Glomerular sclerosis can be a late finding
j Streptococcus pneumoniae (Neuraminidase
Clinical features
producing)
Inherited: • Sudden onset of pallor, irritability and weakness
j Complement abnormalities
• Oliguria and prostration
j Cobalamin metabolism defect
• Petechiae, but severe bleeding is rare despite very low
j von Willebrand factor-cleaving protease
platelet counts
deficiency • Renal insufficiency rapidly evolving into renal failure.
Autoimmune: j Hyperkalemia
j Scleroderma j Volume overload
j Systemic lupus erythematosus j Hypertension
Drugs: j Severe anemia
j Tacrolimus • Cardiac involvement is rare
j Cyclosporine A j Arrhythmias
j Quinine j Heart failure
Misc: j Pericarditis
j Postrenal transplant j Myocardial dysfunction
• Central nervous system (CNS) involvement in
D+ HUS (Diarrheal type) ≤20% of cases.
• Affects children less than 2–3 years of age j Irritability, lethargy, altered sensorium or
• Preceded by Acute diarrhea or dysentery nonspecific encephalopathic features.
• Caused by verotoxin producing E.coli O157:H7 in j Hypoxic Seizures and encephalopathy, secondary
western countries to microvascular cerebral thrombosis.
• In India, Shigella dysenteriae 1 is the chief j Hypertension may produce an encephalopathy
pathogen and seizures.
• Presents with acute onset anemia, irritability and j Focal/Generalized tonic clonic seizures
lethargy • Intestinal complications
D—HUS (Atypical/Nondiarrheal Type) j Intussusception
• Affects older children j Ischemic enteritis
• Insidious onset j Severe inflammatory colitis
• Patients manifest symptoms of streptococcal infection j Bowel perforation
when they develop HUS. j Pancreatitis.
250
mebooksfree.com
Investigations Pathology
• Blood film—Distorted RBC, increased reticulocyte • Focal and segmental mesangial proliferation
count, thrombocytopenia, neutrophilic leukocytosis • Diffuse mesangial IgA and C3 complement
• Comb’s test—Negative in all HUS except deposits
pneumococcal HUS • Excessive amounts of poorly galactosylated
• Urine analysis—Microscopic hematuria and mild IgA1 predisposing to IgG and IgA autoantibody
proteinuria production.
• Increased blood urea and serum creatinine reflecting • Crescent formation and sclerosis in severe cases.
severity of disease Investigations
• Stool Culture • Urine analysis—Microscopic or gross hematuria
• Renal biopsy shows swollen endothelial cell separated • Proteinuria < 1000 mg/24 h
from basement membrane with foamy material in • Serum IgA levels increased in 15% of patients
subepithelial space with narrowing of lumen • Light microscopy—Focal and segmental mesangial
• Partial thromboplastin time and prothrombin time proliferation
will be normal • Electron microscopy—Mesangial deposits
Treatment • Immunofluorescence—Diffuse mesangial deposits
• Approach is early recognition of disease, anticipating of IgA
complications, monitoring and supportive care Treatment
• Basic management is that of renal failure, • Primary goal is to manage hypertension and
Hypertension, Dyselectrolemia, and Anemia proteinuria
• Plasma infusion or Plasmaphersis may benefit HUS • Hypertension—ACE inhibitors
with CNS manifestations • Proteinuria—Angiotensin II receptor antagonists,
• Eculizumab (Anti C5 antibody) used in atypical HUS Corticosteroids
Complications • Renal transplantation
• Acute renal failure Prognosis
• Volume overload • Does not progress to End stage renal disease in
• Encephalopathy childhood
Prognosis • Poor prognostic factors
• Overall outcome of atypical HUS is poor compared j Persistent hypertension
to typical HUS j Reduced renal function
• Mortality rate of typical HUS is <5% j Increasing or prolonged proteinuria
• Factors suggestive of poor prognosis
j Oligoanuria >2 weeks
Severe CNS involvement
15.8 SLE nephritis (Lupus
j
j Presence of renal cortical necrosis

Nephritis)
• Common cause of morbidity and mortality in SLE.

15.7 IgA nephropathy • Renal disease in childhood SLE seen in more than
(berger’s disease) 80% of cases.
Pathogenesis
• Most common chronic glomerular disease in children • Binding of autoantibodies to glomerular
• Mesangial glomerular deposition of IgA in absence components
of systemic disease • Passive “trapping” of circulating immune complexes
• Age group—>10 years with male predisposition • Alteration in innate immunity resulting in
Clinical features inflammation
• Often precipitated within 1–2 days upper respiratory Grading
infection • Class I—Minimal mesangial changes
• Recurrent episodes of gross hematuria • Class II—Mesangial proliferation
• Proteinuria • Class III—Focal proliferative GN (<50% glomeruli
• Presents as nephritic syndrome, nephrotic syndrome, involved)
or a combined nephritic–nephrotic picture • Class IV—Diffuse proliferative GN (>50% glomeruli
• Mild to moderate hypertension involved)
251
mebooksfree.com
• Class V—Membranous GN Causes of hematuria in children

• Class VI—Glomerulosclerosis Upper Urinary Tract Vascular
Clinical features Disease • AV Malformations
• Majority of patients are Adolescent females • Isolated renal disease (aneurysms,
• Common in first year of diagnosis • IgA nephropathy hemangiomas)
• Alport syndrome • Renal vein thrombosis
Normal renal function, hematuria, • Post-infectious GN • Hemoglobinopathy
Class I−III • Membranous • Crystals in urine
proteinuria <1 g/24 h
nephropathy Anatomical
Reduced renal function, hematuria,
• Rapidly progressive GN • Hydronephrosis
Class IV hypertension, proteinuria, nephrotic
Multisystem disease • Polycystic kidney
syndrome
• SLE disease
Class V Nephrotic syndrome • Hemolytic-uremic • Multicystic dysplastic
syndrome kidney
Investigations • Goodpasture • Tumor
• Antinuclear and Anti ds DNA antibodies syndrome • Trauma
in blood • HSP nephritis Lower Urinary Tract
• Renal biopsy—Focal/diffuse GN, Membranous • Wegener Disease
nephropathy granulomatosis • UTI
• Immunofluorescence—Mesangial and sub- Tubulointerstitial disease • Trauma
endothelial capillary wall deposits of IgG, IgA, C3, • Acute tubular necrosis • Bladder tumor
• Pyelonephritis • Stone formation
and C1q (Fig. 15.1)
• Interstitial nephritis • Coagulopathy
Treatment
Class I–II Corticosteroids History of following Examination
symptoms should be asked • Facial puffiness,
Class III–IV Corticosteroids + Cytotoxic agents
• Pain in the flank or Pedal edema
Class V–VI Plasmapheresis, IV immunoglobulin suprapubic region • Pallor
and Rituximab. • Frequency and dysuria • Hypertension
• Facial puffiness • Signs of Volume
• Cytotoxic agents—–Cyclophosphamide, • Edema Overload
Azathioprine, Mycophenolate mofetil • Fever and rash • Bony abnormalities
• Abdominal pain • Palpable abdominal
Prognosis
• Trauma masses
• Renal survival in 80% of patients in the first 10 years
of diagnosis.
Lab investigation
• WHO class IV lupus nephritis exhibit the highest risk
for progression to ESRD.
• Fresh urine specimen is examined for
j Red cells/casts and protein, Dysmorphic RBC
• Risk of malignancy or infertility if a cumulative j Urinary calcium creatinine ratio for hypercalciuria
dose of >20 g of cyclophosphamide or other
immunosuppressants
• Plain X-ray and ultrasound abdomen—to rule out
renal and urinary tract anomalies and calculi
• Blood levels of urea and creatinine
• Renal biopsy—for light microscopy,
immunofluorescence and electron microsocpy
15.9 Approach to hematuria
j Hematuria associated with heavy proteinuria
j History of Renal disease in the family
• Hematuria is defined as the presence of at least 5 red j Evidence of Chronic kidney disease
blood cells (RBCs)/microliter of urine j Persistent Hypertension
• Presence of blood in urine can impart various hues to j Persistent microscopic hematuria
urine, deep red, brown and pink
• Concentrated urine can sometime be mistaken as Causes of persistent microscopic hematuria
hematuria
• Idiopathic hypercalciuria
• Porphyria and beet ingestion and certain drugs like
rifampicin can also lead to red/orange coloured • Benign familial hematuria
• Alport syndrome
urine
• IgA nephropathy
• Uric acid crystals can lead to faint pink color of • Membranoproliferative GN
urine.
252
mebooksfree.com
underlying basement membrane, large proteins such

15.10 Nephrotic syndrome as globulins can leak as well.
Clinical features
• Nephrotic syndrome is a common childhood • Age of onset—2−6 years with male predisposition
glomerular disease presenting with heavy (nephrotic- (2:1 ratio)
range) proteinuria. • Insidious onset with peri-orbital facial puffiness
• Characterized by the classic tetrad of findings (Fig. 15.6) and pedal edema. Edema progresses
j Massive proteinuria (> 1 gm/m2 /day or >3.5 g/ to involve extremities, trunk, Abdomen (Ascites),
day or urine protein creatinine ratio >2) pleura (hydrothorax) and genitalia. Some cases
j Hypoalbuminemia (less than 2.5 g/dL) present with whole body edema (Anasarca).
j Hyperlipidemia (Serum cholesterol >200 mg/dL). Secondary effects like respiratory distress due to
j Edema hydrothorax and ascites can be seen.
• Majority of Nephrotic syndrome are idiopathic • Anorexia, irritability, abdominal pain and diarrhea
Causes of Nephrotic syndrome are common
• Decreased urine output
Idiopathic Nephrotic Secondary causes • Blood pressure is normal
syndrome • Infections
• Minimal change j Endocarditis
Edema
disease (Most j Hepatitis B, C, • Exact mechanism of edema formation not known
common) HIV-1 • There are 2 opposing theories,
• Focal segmental j Malaria j The underfill hypothesis: Hypoalbuminemia—
glomerulosclerosis j Toxoplasmosis, Decreased oncotic pressure -> leakage of plasma
• Membranous Schistosomiasis into interstitium, causing edema—reduced
nephropathy • Drugs intravascular volume—↑vasopressin, atrial
Genetic causes j Captopril natriuretic factor and aldosterone—↑ sodium and
• Finnish-type j Penicillamine water retention in tubules
congenital nephrotic j NSAIDs j This hypothesis however does not explain
syndrome (absence of • Immunologic or intravascular volume overload seen in some
nephrin) Allergic Disorders patients
• Focal segmental j Vasculitis
j The overfill hypothesis: Primary sodium
glomerulosclerosis syndromes retention—volume expansion—leakage of excess
(mutations in j Food allergens
fluid into interstitium
nephrin, podocin) j Serum sickness
j This hypothesis does not explain the obvious
• Diffuse mesangial • Associated With
intravascular volume depletion seen in most patients.
sclerosis Malignancy
• Denys-Drash j Lymphoma Hyperlipidemia
syndrome j Leukemia • Increase in cholesterol, triglycerides, LDL and VLDL.
• Due to increased hepatic synthesis of lipoproteins in
response to hypoalbuminemia
15.10.1 Minimal change disease/ • Decreased catabolism of lipids due to urinary loss of
lipoprotein lipase
steroid sensitive nephrotic
Increased Susceptibility to Infections
syndrome
• At risk of developing infections such as cellulitis,
Pathogenesis (Fig. 15.5) bacteremia and spontaneous bacterial peritonitis.
• Increased permeability of glomerular capillary wall is • Possible explanation includes
basic abnormality in nephrotic syndrome. Podocytes j Hypoglobulinemia due to urinary losses of
are epithelial cells of the glomerular capillary loop. immunoglobulin (Ig G)
Foot processes of a podocyte are connected by slit j Urinary loss of complement factors C3 and C5
diaphragm. Components of slit diaphragm inlcude lead to impaired opsonization
nephrin, podocin and α-actinin 4. Foot process and • Increased risk for infection with encapsulated bacteria
slit diaphragm forms glomerular filtration barrier for • Spontaneous bacterial peritonitis
proteins. Podocyte injury leading on to its effacement j Presents with fever, abdominal pain, and
or genetic mutations of genes producing podocyte peritoneal signs.
proteins may cause nephrotic-range proteinuria j Peritoneal leukocyte counts >250 cells/uL are highly
• Proteins of low molecular weight like albumin are suggestive of spontaneous bacterial peritonitis.
preferentially filtered by the glomeruli than those of j Pneumococcus is the most frequent cause, rarely
high molecular weight. However if there is damage to Gram-negative bacteria
253
mebooksfree.com
Approach to Hematuria—algorithm
Hypercoagulability Laboratory findings

• Results from multiple factors: • Nephrotic Range proteinuria
j Vascular stasis due to hemoconcentration and j Proteinuria (>1 g/m2 /24 h or >3.5 g/24 h)
intravascular volume depletion j Spot urine protein creatinine ratio (PCR) > 2.0
j Increased platelet counts and aggregability • Urine analysis—Proteinuria (3+ or 4 +), Hyaline or
j Increased levels of fibrinogen Granular cast
j Antithrombotic factors such as antithrombin III • Microscopic hematuria in few patients, Urine C/S
and protein S are lost in urine • Hypoalbuminemia (≤2.5 g/dL)
• Deep venous thrombosis can occur • Hypercholesterolemia (>200 mg/dL).
254
mebooksfree.com
Figure 15.5 Pathophysiology of Nephrotic Syndrome. Source: BRENNER and RECTOR’S The Kidney, 2004
• Blood urea, serum creatinine and serum electrolytes • Immunofluorescence—Mesangial IgM deposits
are normal • Chest X-ray, Tuberculin test—To rule out tuberculosis
• Levels of IgG is low and IgM is high, C3 is normal before starting steroids
• Light microscopy: Normal
• Electron microscopy: Effacement of Foot processes Indications of Renal Biopsy
• Age at onset less than 1 year or more than 16 years
• Gross or persistent microscopic hematuria, or
low C3
• Renal failure, not attributed to hypovolemia
• Suspected secondary cause
• Sustained hypertension.
Important definitions
• Remission Urine albumin nil or trace

(proteinuria < 4 mg/m2/h, Spot PCR < 0.2) for
three consecutive early morning samples
• Relapse Urine albumin 3+ or 4+ (or
proteinuria > 40 mg/m2/h) for three consecutive
early morning specimens, having been in remission
previously
• Frequent relapses Two or more relapses in initial
6 months or more than three relapses in any 12
months
• Steroid resistance Absence of remission despite
therapy with daily prednisolone at a dose of 2 mg/
kg/day for 4weeks
• Steroid dependence Two consecutive relapses
when on alternate day steroids or within 14 days of
its discontinuation
Figure 15.6 A child with nephrotic syndrome.
255
mebooksfree.com
Management algorithm
Treatment • Infections—Pneumonia, Peritonitis, Cellulitis,

• High protein diet Meningitis are common
• Salt restriction j Pneumococcus
• Diuretics to reduce edema—Furosemide 1−4 mg/kg/ j Gram-negative organism
day in 2 divided doses j Varicella
• Steroids are mainstay therapy in nephrotic syndrome. • Thrombosis of renal, pulmonary and cerebral veins
Prednisolone is the drug of choice. Prednisolone is • Hypovolemia and Acute renal failure
started at 60 mg/m2/day or 2 mg/kg/day for 4–6 weeks. • Steroid toxicity—Cushingoid facies, Fluid retention,
Once child responds and edema disappears completely Hypokalemia, Hypertension, Gastritis, Infections, and
(usually takes 4−6 weeks), maintenance treatment Osteoporosis
with alternate day low dose prednisolone is started Prognosis: Remission in >95% cases and good prognosis
(40 mg/m2 / day or 1.5 mg/kg/day).
• Treatment of associated infections. 15.10.2 Steroid resistant nephrotic
• Dyslipidemia—Amount of fat should be limited in
diet(Fat should contribute to <30% of calories while syndrome
saturated fat contributes <10% calories) Clinical features
• Relapses are frequent • Affects older children
Complications • Patients may present with hematuria and hypertension
• Edema • Renal biopsy shows C3, immunoglobulin deposits
256
mebooksfree.com
• Unsatisfactory response to steroids and poor • Rickets

prognosis • Nephrolithiasis
Treatment Diagnosis
• Aim of therapy is to maintain remission of proteinuria • Hyperchloremic metabolic acidosis
• Best regimen—Combining calcineurin inhibitors and • Hypokalemia
tapering dose of steroids • Increased urinary excretion of calcium
• Adjuvant therapy with ACE inhibitors will decrease • Decreased urinary citrate
proteinuria and hypertension • Urine pH >5.5
• IV albumin can be given in symptomatic • Measurement of difference between urinary and blood
hypovolemia, edema and marked ascites CO2 is reduced in distal RTA (below 10 mm Hg)
Prognosis • Hearing evaluation
• Minimal change nephrotic syndrome will have Treatment
excellent prognosis
• Frequency of relapses will decrease with time • Acidosis—Sodium bicarbonate therapy (2−3 mEq/
kg/day)
• Steroid resistant nephrotic syndrome often develops
progressive renal insufficiency leading to poor • Treatment of acidosis reduces potassium loss and
promotes growth and healing of rickets
prognosis
• Hypokalemia should be treated
• Some patients require potassium replacement for
longer time
15.11 Renal tubular acidosis • Hypercalciuria—thiazide diuretics
B) Type 2—Proximal RTA
• Group of disorders characterized by defect in renal Pathophysiology
acidification resulting in hyperchloremic metabolic • Due to reduced proximal tubular reabsorption of
acidosis and high urine pH bicarbonate
• Defects in tubular transport leads to decreased • This leads to marked bicarbonaturia
tubular absorption of bicarbonate and distal • Distal acidification mechanism is intact so acidosis is
secretion of hydrogen ions results in impaired of less severity
capacity of net acid excretion • Proximal RTA may be isolated or generalized
• Anion gap is in normal range 8−12 mEq/L proximal tubular dysfunction (Fanconi syndrome)
• Renal function is normal or mildly reduced • Fanconi syndrome can be
• Four types of RTA are recognized j Idiopathic
j Type 1 (Distal) j Secondary to metabolic disorder
j Type 2 (Proximal) isolated/Fanconi syndrome j Drugs and toxins
j Type 3 (Combined) j Tubulointerstitial nephritis
j Type 4 (Hyperkalemia)
Clinical features
A) Type 1 (Distal RTA) • Failure to thrive
Pathophysiology • Physical retardation
• Occurs due to deficiency of secretion of hydrogen ion • Irritability
by distal tubule and collecting duct • Anorexia and listlessness
• Defective secretion of H+ in distal tubule in absence • Symptoms related to hypokalemia
of decrease in GFR
• Causes low excretion of ammonium ions and Diagnosis
titratable acidity • Blood pH and HCO−3 levels are low and urine
• Hypokalemia is produced by increased urinary loss of pH < 5.5
potassium and aldosterone stimulation • Demonstration of high fractional excretion of
• Condition is sporadic, but may be inherited bicarbonate following bicarbonate infusion is
(dominant, recessive or X—linked) confirmatory
• Disease associated are SLE, Wilson disease or • Evaluation of aminoaciduria, glucosuria, proteinuria
secondary to renal disease are done
Clinical features
• Other associated disorders screening should be done
• Failure to thrive Treatment
• Polyuria • Acidosis should be corrected with bicarbonate
• Polydipsia (5−20 mEq/kg)
• Hypokalemic muscle weakness • One part is given as potassium citrate
257
mebooksfree.com
• Children with Fanconi syndrome need phosphate • Constipation

supplements • Repeated catheterization
• Vitamin D necessary for children with rickets • Congenital anomalies of urinary tract
• Obstructive uropathy
Proximal Classic Type 4 • Neurogenic bladder
RTA Distal RTA RTA • Immuno suppressive drugs
Plasma Normal Normal or High Pathophysiology
potassium or low low • All UTI are essentially ascending infections. Bacteria
Urine pH < 5.5 >5.5 <5.5 from fecal flora, colonizes perineum and enter the
Urine anion Gap Negative Positive Positive bladder then to kidney.
Urine Low Low Low
• Papillae in kidney have anti-reflux mechanism
that prevents urine entering collecting duct. Some
ammonium
compound papillae allow anti reflux resulting intra
Fraction >10%– <5% >5%–10% renal reflux. Infected urine stimulates immunogenic
bicarbonate 15% and inflammatory response leading to renal injury
excretion and scarring
Urine blood >20 <20 >20 Clinical features
PCO2
• Depends upon age and severity
Urine calcium Normal High Normal or • Neonates
low j Sepsis with fever
Other tubular Often Absent Absent j Vomiting, diarrhea
defects present j Jaundice
Nephrocalcinosis Absent Present Absent j Poor weight gain and lethargy
Bone disease Common Often Absent • Older children
present j Unexplained fever
j Frequency and urgency of micturition
j Hypogastric pain
j Foul smelling urine
15.12 Urinary tract infection
Complicated UTI Simple UTI
• Urinary tract infections (UTI) are among the most • High grade fever • Low grade fever
common infections of childhood. UTI can present • Systemic toxicity • Dysuria
with nonspecific or minimal features and can easily • Persistent vomiting • Urgency
• Dehydration • Frequency
be missed. Untreated UTI can progress to cause renal
• Raised creatinine
parenchymal damage with scarring, hypertension and
chronic kidney injury. Diagnosis
• Boys have higher incidence in first year of life. After • Gold standard test to diagnosis UTI is urine culture.
2 years girls are 10 times more commonly affected Clean catch sample showing > 105 CFU/mL is
• Classified based on site of involvement considered as significant bacteriuria
Upper UTI
j
• Any colonies on suprapubic bladder aspiration
– Pyelonephritis and > 50,000 CFU/mL on urethral catheterization
– Ureteritis in < 2 years children are considered significant
Lower UTI
j
• Dipstick test detecting nitrites and leukocyte esterase
– Cystitis
• Asymptomatic bacteriuria—Absence of symptoms
– Urethritis with significant bacteriuria
Causative organisms
• Urinalysis
• E.coli (most common) j Not a substitute for urine culture
• Proteus (common in boys) j Presence or Absence of urinary white cells alone is
• Klebsiella not reliable feature of UTI
• Enterobacter j Absence of pyuria does not preclude the need for
• Staphylococcus saprophyticus urine culture.
• Pseudomonas • Imaging studies (Ultrasound, DMSA, micturating
Predisposing factors cystourethrogram) are indicated in first episode of
• Female sex (except during infancy) culture positive UTI under the age of 1 year and
• Severe VUR recurrent UTI in older children
258
mebooksfree.com
Guidelines for imaging in children following UTI (IAP 2011)
Treatment • VUR can lead to progressive renal damage and

• Asymptomatic bacteriuria does not require treatment. scarring in the presence of UTI
In symptomatic UTI, the major aim is to prevent renal • Predisposes to development of
scarring and its complications. j Acute pyelonephritis
• Children less than 3 months and those with j Reflux nephropathy
complicated UTI should be hospitalized and receive Etiology
parenteral antibiotics
• Primary VUR
• Amount of oral fluids should be increased and j Autosomal dominant condition.
child should be encouraged to frequently empty j Valve at the uretero-vesicle junction preventing
bladder. retrograde flow of urine is defective.
• Cephalosporins and aminoglycosides are safe and • Secondary VUR—High intravesical pressure seen in
effective drugs for empirical therapy. Oral drugs for j Neurogenic bladder (Myelomeningocele/Spinal cord
empirical therapy include amoxicillin, cotrimoxazole injury)
and nitrofurantoin. Drugs are modified based on j Bladder outlet obstruction (Posterior urethral valve)
organism growth in urine culture and sensitivity j Bladder dysfunction (Dysfunctional voiding)
pattern
Clinical features
• Duration of treatment should be for a minimum
period of 10–14 days. However, older children • Familial—30%−35%
and simple UTI should receive oral antibiotics for • Recurrent febrile urinary tract infection
7–10 days. Adolescents with cystitis receive antibiotics • Chronic acidosis
for minimum 72 h • Hypertension
• Renal insufficiency
Imaging studies
• Combination of USG abdomen, MCU, and Diagnosis
radionuclide renal scan is recommended • Radio nuclide cystogram—More sensitive and specific
• USG detects major renal anomalies • Radio contrast Miciturating cystourethrogram
• MCU detects presence of VUR and posterior urethral • DMSA—to detect renal scarring
valve Grading of vesicouretric reflux (Fig. 15.7)
• Renal cortical 99mTc DMSA scans—diagnose Grade I—Reflux limited to ureter (no dilatation)
pyelonephritis and renal scars Grade II—Reflux upto pelvis. calyces not dilated and
fornices are normal
15.13 Vesico uretric reflux (VUR)
• Retrograde urinary flow from bladder into upper

urinary tract during micturition. Underlying
pathology includes incompetence of uretero−vesical
junction due to shortening and lack of obliquity of
submucosal and intravesical segments
• Increase in intravesical pressure transmitted to ureter
and renal pelvis. Urine enters collecting duct and
renal tubules. Pathogenic organisms enter renal
parenchyma resulting in inflammation and renal
scarring. Figure 15.7 Grading of VUR.
259
mebooksfree.com
Grade III—Reflux + Mild dilatation of Ureter ± blunting Pathophysiology

of fornices. • Prerenal
Grade IV—Reflux + Moderate dilatation of Ureter and j Characterized by reduced circulating arterial
calcyes ±, blunting of fornices but presereved papillary volume leading on to decreased renal perfusion
impressions and Glomerular filtration rate
Grade V—Reflux + Severe ureteral dilation and tortuosity j There are no features of direct renal damage
and loss of fornices and papillary impression j Commonly seen in conditions with vomiting and
diarrhea
Treatment
• Intrinsic Renal
• Aim is to prevent pyleonephritis, VUR related renal j Persisting hypoperfusion and ischemia can
injury, other complications
develop into intrinsic renal parenchymal damage
• Antibiotic prophylaxis is recommended for all j Prolonged ischemia/hypoxic injury leads to acute
children with VUR
tubular necrosis (ATN)
j Cotrimoxazole or nitrofurantoin are antibiotics
j ATN is associated with intrarenal hemodynamics
used
alteration, tubular obstruction and backward flow
j Cephalexin used in 4−6 months child
of glomerular filtrate into peritubular capillaries
• Prophylaxis continued till the child is free from UTI/
Reflux for 6 months
• Post renal
j Wide spectrum of disorders associated with
• Surgery is indicated in obstruction of urinary tract
j Severe VUR (grade IV or V) persisting beyond
j Recovery of renal function occurs after obstruction
2 year of age
is relieved
j Noncompliance or intolerance to medication
j Appearance of new renal scars Staging of Acute Kidney Injury
j Deterioration of renal function
j Multiple recurrent UTI despite prophylaxis AKN Serum creatinine Urine output
• General measures Stage criteria criteria
Liberal fluid intake
1 Increase in serum Less than 0.5 mL/
j
j Regular and complete bladder emptying creatinine >0.3 mg/ kg/h for > 6 h
j Constipation should be avoided dL or >150% to 200%
Long—Term prophylaxis from baseline
1. Children below 3 year of age received treatment for 2 Increase in serum Less than 0.5 mL/
first UTI and investigated for underlying etiology creatinine more than kg/hour for > 12 h
2. Children with normal urinary tract and no VUR, but 200% to 300% from
with three or more UTI in 1 year baseline
3. UTI with VUR. 3 Increase in serum Less than 0.3 mL/
creatinine >4.0 mg/ kg/h for 24 h or
dL or more than 300% anuria for 12 h
15.14 Acute renal failure from baseline
• Sudden worsening in kidney function resulting in the Clinical features

inability to maintain fluid and electrolyte homeostasis • In a suspected case, well taken history and
Causes examination often clinches the diagnosis. In a child
with vomiting, diarrhea or any other fluid loss,
Prerenal Intrinsic Renal Postrenal prerenal AKI should be suspected. Intrinsic renal AKI
• Acute gastro- • Glomerulo- • PUJ obstruc- should be suspected in cases of glomerulonephritis
enteritis nephritis tion (Edema, hypertension and bloody urine) and
• Severe dehy- • HUS • Posterior Acute tubular necrosis (prolonged hypotension
dration • Acute tubu- urethral valves or exposure to nephrotoxic drugs). Children with
• Hemorrhagic lar necrosis • Hemorrhagic evidence of urinary tract obstruction (hydronephrosis,
shock • Renal vein cystitis vesicoureteric reflux, recurrent UTI) are at risk for
• Septic shock thrombosis • Tumor postrenal AKI.
• Hypoalbu- • Tubuloint- • Ureterocele • Dehydration is present in cases of hypovolvemia
minemia erstitial • Urinary leading to prerenal AKI. Fluid overload is seen with
• CCF nephritis stone glomerulonephritis and ATN.
• Nephrotoxic • Neurogenic
• Oliguric phase typically last for 3−10 days.
drugs bladder
Biochemical and clinical abnormalities worsen during
260
mebooksfree.com
oliguric phase. Oliguric phase is followed by diuretic • Dopamine can cause renal vasodilation and induce
phase characterized by improving urine output which moderate diuresis and natriuresis
lasts for a week. Water and electrolytes especially Fluid repletion
potassium is lost in diuretic phase
• Prerenal ARF responds to fluid replacement.
Approach to diagnosis Dehydration is corrected by 20−30 ml/kg of normal
• History of diarrhea, vomiting, fluid or blood loss is saline or ringer lactate over 45−60 mins. Responding
noted patients will have increase in urine output (2−4 mL/
• Fluid intake of last 24 h is calculated kg over 2−3 h). In case of no diuresis after
• Urine output is not reduced in nephrotoxicity/ administering fluids, furosemide (2−3 mg/kg IV)
intravascular hemolysis challenge is given
• In prerenal azotemia tubular function is intact, • If patient fails to pass urine inspite of fluid and
reabsorption of water and sodium increased diuretic challenge, a diagnosis of intrinsic AKI is made
• Impaired tubular function will result in increased • If bleeding is present, blood transfusion should be
sodium excretion and failure to concentrate urine given
• Determination of urine sodium and osmolality Fluid restriction
and fractional excretion of sodium will help to
differentiate prerenal and intrinsic renal failure • In established intrinsic AKI, fluid restriction is
required. Daily fluid requirement is restricted to
Investigations
insensible water losses (400 mL/m2/day), urine
• Blood—Complete blood counts show dilutional or output and extra renal fluid losses. Usually given
hemolytic anemia; Leukopenia or thrombocytopenia
orally and intravenous fluids not required. Sodium
• Reduced C3 levels seen in poststreptococcal levels should be monitored and presence of
glomerulonephritis
hyponatremia indicates overhydration
• Renal function - Elevated urea and creatinine
• Electrolytes - Hyponatremia, Hyperkalemia, Treatment of complications
Hypocalcemia, Hyperphosphatemia • Fluid overload—Fluid restriction as mentioned
• Arterial blood gas analysis—Metabolic acidosis above
• Urine—Urinalysis, culture, sodium osmolality, • Pulmonary edema—Oxygen, Frusemide 2−4 mg/kg IV
fractional excretion of sodium • Hypertension
• Chest x ray—for evidence of fluid overload j Symptomatic: Sodium nitroprusside 0.5−8.0
• Ultrasound abdomen—for evidence of ascites, mcg/kg/min infusion, frusemide 2−4 mg/kg iv,
features of urinary tract obstruction nifidipine0.3−0.5/kg oral/sublingual
• Specific investigation to determine cause j Asymptomatic: Nifidipine, amlodipine, prazosin,
j Blood smear, platelet and reticulocyte labetalol
count, C3 and LDH levels, stool shiga toxin • Metabolic acidosis—No treatment required. If
(suspected HUS) severe (pH <7.15) Sodium bicarbonate IV or oral (if
j Blood ASO, C3, ANA, antineutrophil cytoplasmic bicarbonate <18 mEq/L)
antibody (suspected AGN/RGPN) • Hyperkalemia—IV Calcium gluconate 0.5−1 mL/
j Doppler ultrasonography (suspected arterial or kg, IV Sodium bicarbonate 1-2 mEq/kg, salbutamol,
venous thrombosis) sodium bicarbonate, Potassium binding resin
j Renal biopsy—Unknown etiology (kayexalate gel)
• Newer biomarkers to assess renal function—Cystatin • Hyponatermia—Fluid restriction, if altered sensorium
C and Neutrophil gelatinase associated lipcalin or Na <125 Meq/L—3% saline 6−12 mL/kg over
30−90 min
Management
• Includes treatment of life threatening complications, • Hypocalcemia—Lowering serum phosphate (low oral
intake and phosphate binders)
maintenance of fluid and electrolyte balance and
nutritional support • Hyperphosphatemia—Phosphate binders
• Diet must contain 1.0–1.2 g/kg of protein in infants • Severe anaemia—Packed red cells 3−5 mL/kg
and 0.8−1.2 g/kg in older children and minimum Dialysis
60−80 kcal/kg • Indication for dialysis in AKI
• Vitamins and micronutrients are supplemented j Anuria/oliguria
General measures j Volume overload with evidence of hypertension/
• Accurate records of daily weight, intake and output pulmonary edema
should be maintained j Persistent Hyperkalemia
• Measures to prevent infection are necessary j Severe metabolic acidosis
• Drugs interfering with renal function should be avoided j Uremia
261
mebooksfree.com
Peritoneal dialysis Causes

• Easy to perform even in neonates and infants. • Glomerulonephritis
Initial renal replacement therapy for sick and j Idiopathic—FSGS
unstable neonates. Peritoneal access is obtained and j Secondary to SLE, IgA nephropathy, HSP
dialysis fluid 30−50 mL/kg left in peritoneal cavity • Reflux nephropathy—primary, secondary
for 30−60 min and then drained using siphon • Obstructive uropathy - PUV, pelviureteric junction
effect. Initial dialysis cycle are of short duration obstruction, renal stones
20−30 min • Developmental anomalies - bilateral renal
• Most important complication—peritonitis hypoplasia, dysplasia
Hemodialysis • Familial nephropathy—nephronophthisis, alport
syndrome, polycystic kidney
• Efficient for correction of fluid and electrolyte • Others—HUS, amyloidosis, renal vein thrombosis,
abnormalities. Expensive and not suited for unstable
renal cortical necrosis
patients and young children. Vascular access is
achieved by double lumen catheter in central line. Pathogenesis
Duration is 3−4 h and 3 times a week • In addition to progressive injury caused by
Continuous renal replacement therapy structural, metabolic or genetic disease the renal
injury itself can progress even after removal of
• Extracorporeal blood purification therapy. Used in
offending agent
sick and unstable patients
Outcome • Hyperfiltration injury is common pathway for
glomerular destruction. As nephrons are lost, the left
• ARF carries mortality rate of 20%−40%
over nephrons undergo hypertrophy with increase
• Septicemia, HUS with prolonged anuria carries worst
in glomerular blood flow. This compensation of
prognosis
surviving nephrons can cause progressive damage
• Other poor prognostic factors are infections and
cardiac, hepatic, and respiratory failures • Proteinuria can cause decrease in renal function by
having direct toxic effects on tubular cells
• Satisfactory outcome with acute tubular necrosis
• Hypertension can exacerbate disease progression by
causing arteriolar nephrosclerosis
• Hyperphosphatemia precipitates deposition of
15.15 Chronic kidney disease calcium phosphate in the interstitium and renal
vessels
(previously known as chronic
renal failure) Clinical features
• Progressive renal failure occurs. Loss of urinary
concentration ability leads to frequent urination,
• CKD refers to progressive, irreversible, gross nocturia and increased thirst. Normocytic
deterioration in renal function, leading on to end- normochomic anaemia.
stage renal disease. Renal damage should last for at
• Growth failure due to resistance to growth hormone.
least 3 months to make a diagnosis of CKD. Anorexia, malnutrition and skeletal deformities are
• Characterized by structural and functional present.
abnormalities with or without decreased GFR
• Hyperphosphatemia and secondary
• Renal maturation occurs from infancy to age of 2, hyperparathyroidism
CKD applies to children > 2years
• Hypertension, severe proximal weakness and
• Divided into 5 stages based on GFR peripheral neuropathy
Stages of CKD • Infection are common
GFR mL/ Investigations
Stage min/1.73 m2 Description • Complete hemogram showing normocytic
normochromic Anemia
1 90 Renal damage with
• Elevated blood levels of urea, creatinine and uric
normal or increased GFR
acid
2 60−89 Renal damage with mild • Arterial blood gas analysis: Reduced bicarbonate and
reduction of GFR pH (metabolic acidosis)
3 30−59 Moderate reduction of • Electrolytes: Hyponatremia, Hyperkalemia,
GFR Hypocalcemia, Hyperphosphatemia
4 15−29 Severe reduction of GFR • GFR is evaluated by inulin clearance, creatinine
5 Renal failure clearance, Cystatin C and iohexol
<15 or dialysis
• Appropriate imaging studies are done
262
mebooksfree.com
Management
CKD treatment focus on following principles 15.16 Renal replacement
• Treatment of reversible renal dysfunction therapies (RRT)
j Includes obstruction in tract, recurrent UTI, and
decreased renal perfusion • RRT is needed in the setting of acute renal
j Avoid nephrotoxic drugs and radiocontrast dyes dysfunction and chronic kidney disease
• Retarding progression of renal failure • RRT is considered when GFR falls below 12 mL/
j Hypertension should be controlled with beta min/1.73 m2
blockers and calcium channel blockers • Common indications to initiate RRT
j ACE inhibitors reduces proteinuria j Fluid overload, hypertension, gastrointestinal
• Diet symptoms
j Diet rich in polyunsaturated fatty acids and j Uremic complications (Encephalopathy,
medium chain triglycerides pericarditis, platelet dysfunction and bleeding)
j Proteins 1−2 g/kg/day is given j Severe dyselectrolemia (Hyperkalemia)
j Sodium intake is individualized as renal j Refractory acidosis
absorption is impaired • Different forms of RRT
j Diet rich in potassium are avoided j Peritoneal dialysis
j Calcium supplements are given as calcium j Hemodialysis
carbonate or acetate j Renal transplantation
j Dairy products are avoided to reduce phosphate
Peritoneal dialysis
intake
j Vitamin B1, B2, folic acid, pyridoxine, and B12 are
• Preferred in infants and young children.
Peritoneum functions as the semipermeable
supplemented
membrane for exchange of solutes and fluids. Done
• Anemia is treated with iron 4−6 mg kg/day and
through a Tenckhoff catheter tunneled through
subcutaneous injection of erythropoietin increase
abdominal wall into peritoneum. Dialysate fluid
hemoglobin levels.
can be administerd manually or with automatic
• Urinary tract infection and other infections are treated
cycler. Duration of dialysis is 10–12 h during
with less toxic drugs
which 4−6 cycles are performed. Procedure can be
• Recombinant growth hormone given to improve
carried out at home by family members with basic
growth velocity in children with chronic renal
training.
failure
• Complication—Peritonitis
• Mineral bone disease
• Contraindication–Abdominal sepsis
j Due to decreased absorption of calcitriol leads to
secondary hyperparathyroidism in CKD Hemodialysis
j Bone pain, muscle weakness, growth retardation • Children require vascular access either arteriovenous
and skeletal deformities are prominent fistula, graft or double lumen indwelling catheter in
j Blood investigations reveals hypocalcemia, central vein (Internal jugular, femoral or subclavian
hyperphosphatemia, raised alkaline phosphate vein). Procedure is technically difficult and not
levels and parathyroid hormone suitable in infants and young children. Dialysis
j X-ray shows metaphyseal changes suggestive of done for 3−4 hours/session with frequency of
rickets 3 session/week. Anticoagulation of the circuit
j Treatment is dietary restriction of phosphate achieved by systemic heparinization. Procedure
and administration of phosphate binders and requires trained technical expertise and continuous
vitamin D monitoring.
• Children should receive all routine immunization. • Complications
In addition they must receive vaccines for j Hypotension due to blood loss into the circuit
pneumococcal, chicken pox, and hepatitis A and B j Infection
• Renal replacement therapy j Dysequilibrium syndrome—Nausea, vomiting,
headache, and convulsions probably due to
Prognosis relatively quick removal of urea from blood than
• Rate of deterioration of renal function in CKD compared to brain.
is variable. In some disorders like HUS, cresentric Renal transplantation
GN, Stage V CKD presents rapidly within few weeks • Suitable for children with end stage 5 CKD
to months. In most other conditions, deterioration • Adult kidney can be transplanted to children
in renal function occurs slowly over a period of few • Children need lifelong immunosuppressive therapy
years. to prevent rejection of graft
263
mebooksfree.com
• Immunosuppressive therapy combination 15.7.2 Autosomal dominant

j Calcineurin inhibitor—cyclosporine or polycystic kidney disease
tacrolimus
j Purine synthesis inhibitor—azathioprine or • Mutation in ADPKD1 (chromosome 16) and ADPKD
mycophenolate mofetil 2 (chromosome 4) genes encoding polycystin 1 and
j Prednisolone polycystin 2 respectively
• Complications • These proteins regulate tubular and vascular
j Rejection of graft development
j Infections Pathology
j Vascular thrombosis • Both kidneys are enlarged
j Recurrence of original disease • Cortical and medullary cysts originating from all
j Malignancy regions of the nephron.
• Pediatric transplant recipients have 1 year survival Clinical features
rate of 90% and 5 year survival rate of 70%. • Usually presents in third or 4th decade of life. Cases
presents with hematuria, hypertension, palpable
kidney and decline in renal function. Enlarged
15.17 Polycystic kidney disease kidneys with multiple cysts are characteristic.
Investigations
• Ultrasound abdomen shows multiple and variable
• Two distinct patterns of inheritance have been sizes of cysts in kidney
described –
Associations
j Autosomal dominant form
j Autosomal recessive form • Cysts in liver, spleen and pancreas
• Mitral valve prolapse
• Berry aneurysms causing subarachnoid bleed
15.7.1 Autosomal recessive Treatment
polycystic kidney disease • Primarily supportive
• Infantile polycystic disease • Control of Hypertension
ACE inhibitors
• Mutation in PKHD1 gene encoding fibrocystin or
j
Angiotension 2 receptor antagonist

polyductin present in chromosome 6
j
• Characterized by fusiform dilatation of collecting

tubules from cortex to medulla
15.18 Posterior urethral valve
Pathology
• Both kidneys are strikingly enlarged
• Most common cause of obstructive uropathy in
• Numerous cysts in cortex and medulla. children
• Dilated, ectatic collecting ducts radiating from the
medulla to the cortex
• Posterior urethral valves are tissue leaflets obstructing
the lumen of prostatic urethra
• Progressive interstitial fibrosis and tubular atrophy
• The prostatic urethra dilates and the bladder muscle
• Congenital hepatic fibrosis—Ductal plate abnormality undergoes hypertrophy.
leading to bile duct proliferation and ectasia
Clinical features
Clinical features
• Dribbling of urine
• Presentation usually occurs in neonatal period. • Abnormal urinary stream
Oliguria, respiratory distress and palpable renal mass
• Palpable bladder
are seen. Cases can be associated with pulmonary
• Recurrent UTI
hypoplasia and characteristic facies (Potter sequence).
Diagnosis
Young children present with hypertension renal
insufficiency and enlarged kidneys
• Antenatal ultrsound
j Bilateral hydronephrosis
Investigations j Distended bladder
• Investigation of choice is ultrasonography which j Severe obstruction—oligohydramnios
shows enlarged bright kidney with/ without visible • Voiding cystourethrogram
cyst j Dilated posterior urethra and valves
Complications j Distended bladder
• Portal hypertension • Perineal ultrasonography
• Hepatic fibrosis • Renal function and anatomy of upper urinary tract
• Chronic kidney disease should be evaluated
264
mebooksfree.com
Treatment
Favorable prognostic factors Online supplementary materials:

• Normal antenatal USG 18−24 weeks of gestation
• Serum creatinine level <0.8−1.0 mg/dL after bladder
decompression
• Renal ultrasound showing cortico-medullary
differentiation
Complications
• Progressive kidney disease
• Bladder dysfunction
265
mebooksfree.com
Chapter | 16 |
Neurology
• Affected children present with bowel, bladder

16.1 Neural tube defects (NTD) dysfunction, paraplegia
• Facial palsy, swallowing difficulty, impaired
tongue movements and laryngeal stridor are
• Most common congenital anomalies of the CNS seen in cases associated with Arnold Chiari
resulting from failure of spontaneous closure of
malformation
neural tube between 3rd and 4th week of fetal life
Etiology
• Spectrum of neural tube defects include
j Anencephaly (Figure 16.1a)
• Multifactorial inheritance – Absent calvarial tissue in brain
• Maternal risk factors – Occurs due to defective closure of rostral
j Folate deficiency
neuropore
j Alcohol exposure
– Most cases die in-utero
j Radiation exposure
– Associated with polyhydramnios
j Insulin dependent diabetes mellitus
j Encephalocele
j Drugs like carbamazepine, valproate
– Herniation of brain and meninges through
j Zinc deficiency
calvarial defect
j Malnutrition
j Meningocele
• Fetal risk factors – Meninges herniate through defect in the
j Trisomy 13, Trisomy 15
posterior vertebral arches.
Pathogenesis
– Transillumination is positive
• All the three primary germ layers develop by 3rd week – Associated with hydrocephalus
of intra uterine life
– Lesions with leaking cerebrospinal fluid or a
• The endoderm, especially the notochordal plate very thin skin covering requires immediate
and the intraembryonic mesoderm, stimulates the
surgical correction.
overlying ectoderm to develop the neural plate by 3rd
j Meningomyelocele (Figure 16.1b)
week of fetal life
– Spinal cord along with meningeal covering
• By the 3rd week, invagination of the neural groove is protrudes externally.
finished and the neural tube is formed by separation
– Seen as raw fleshy mass with leaking CSF
from surface ectoderm
– Commonly seen in lumbosacral region
• Failure of any of these normal processes leads to most j Spina bifida occulta
of the NTDs
– Defective vertebral bodies without exposing the
Clinical features spinal cord or meninges.
• Most of the defects are obvious in fetal ultrasound or – No defect is seen in the exterior
at birth – Mostly asymptomatic
• Most common site is lumbosacral region but any • NTDs are associated with other congenital
part of spine may be affected anomalies
266
mebooksfree.com
Neurology Chapter | 16 |
neurologist, neurosurgeon, orthopedician,

physiotherapist and social worker
• Surgery is the mainstay of treatment. It includes
closure of the defect and a Ventriculo-peritoneal
shunt in case of associated hydrocephalus
• Open lesions with draining CSF are closed within
24 hours due to the risk of meningitis
• Lorber’s criteria for selective surgery - Surgery not
done if
j Evidence of paraplegia
j Lesion below L3 level
j Gross associated congenital anomalies
Prognosis
• Early intervention can reduce neurological
morbidity
• Late complications include
j Meningitis, Shunt infection
j Urinary tract infections
j Voiding dysfunction
j Sexual dysfunction
j Delayed neurological problems
j Epilepsy, Progressive hydrocephalus
• Most cases die during neonatal period
Prevention
• Primary Prevention
j Periconceptional folic acid supplementation to all
pregnant mothers
j Prevention dose – 0.4 mg / day
j Reduces risk by 70%
• Secondary Prevention
j Mothers prior previous pregnancy with neural tube
defects should receive 4 mg/ day
j Folate supplementation should be started two
Figure 16.1 A, Anencephaly. B, Meningomyelocele. months before expected conception to first
3 months during pregnancy.
• Most cases die in-utero or in early neonatal period.

Prenatal diagnosis 16.2 Hydrocephalus
• Prenatal diagnosis can be made by ultrasound
examination
• Enlargement of the head secondary to accumulation
• Elevated maternal serum alpha feto protein levels of CSF in the intracranial spaces. The cause may be
during 14 and 16 weeks of gestation
due to increased production, decreased clearance of
• Elevated amniotic fluid alpha fetoprotein and CSF or both.
acetylcholinesterase
• CSF is secreted into lateral ventricles from choroid
Investigations plexus. CSF passes through the foramina of Monro
• Complete blood counts, Blood for cross into the third ventricle and then into the fourth
matching ventricle via aqueduct of Sylvius. CSF enters
• X ray chest,Ultrasound of head and abdomen the subarachnoid spaces through foraminas of
• MRI spine Luschka and Magendie situated in the roof of the
• Culture from lesions and draining CSF fourth ventricle. Only 20% of it enters the spinal
Treatment subarachnoid space. CSF is reabsorbed through the
• Requires multi-disciplinary management involving a arachnoid granulations and then enters dural venous
team of neonatologist, developmental pediatrician, sinsuses.
267
mebooksfree.com
Congenital hydrocephalus
Causes
Congenital Acquired
• Intrauterine infections • TB, Chronic and
like rubella, CMV, pyogenic meningitis
toxoplasmosis, • Post intraventricular
Intracranial bleeds, hemorrhage
Intraventricular • Posterior fossa
hemorrhage tumors like
• Congenital medulloblastoma,
malformations like astrocytoma,
aqueduct stenosis, ependymoma.
Dandy walker syndrome, • Intracranial
Arnold Chiari syndrome hemorrhage and
• Midline tumors ruptured aneurysm.
obstructing CSF flow.
Cause of Hydrocephalus
• Non-obstructive or communicating hydrocephalus
–Occurs due to obliteration of subarachnoid cisterns
or dysfunctional arachnoid villi
j Post hemorrhagic (Most common cause)
j Meningitis
j Achondroplasia
j Choroid plexus papilloma
• Obstructive or non-communicating hydrocephalus
–Occurs due to obstruction within the ventricular
system
j Aqueductal stenosis (Most common cause)
j Infections (Toxoplasma, neurocysticercosis,
mumps)
j Arnold Chiari and Dandy-walker anomalies
j Mass lesions - Abscess, hematoma, tumors and
phakomatosis
Figure 16.2 A, Flow diagram of Cerbrospinal fluid (CSF).
Clinical features
• Cases of congenital hydrocephalus either presents
immediately after birth or after few weeks of
postnatal life. Acquired hydrocephalus develops
much later often in association with risk factor like
postmeningitic sequlae.
• Classical presentation includes excessive increase in
head size, protruding forehead along with wide and
bulging fontanels. Cranial sutures open up and scalp
veins become dilated and more prominent.
• Infants have characteristic ‘Sunset sign’ (Visible
sclera above the cornea - Figure 16.2b). Percussion
of the head reveals cracked pot resonance (Macewen
sign). Transillumination of cranium may be
positive.
• Features of raised intracranial pressure are not
usually seen till anterior fontanelle closes. In older
children, irritability, seizures, papilledema, spasticity,
ataxia, urinary incontinence, and progressive mental
deterioration can occur. Figure 16.2 B, Positive ‘Sun set’ sign.
268
mebooksfree.com
• Loss of brain tissue can be associated with secondary • Abnormal shunting of blood leading to expansion of
compensatory enlargement of the CSF spaces known vessels and space occupying effect or rupture of vein
as ‘Hydrocephalus ex vacuo’ and intra-cerebral bleeding
Diagnosis of Hydrocephalus • Site of lesion
• Serial monitoring of head circumference: > 1 cm j Cerebral hemisphere—Most common location
every 2 weeks in the first 3 months of life. j Brain stem
• Persistent separation of squamoparietal sutures j Spinal cord
Imaging
• Cases present with seizures and migraine like headaches
• Auscultation of the skull reveals high-pitched bruit
• Serial ultrasound monitoring to evaluate ventricular • Rupture of malformation causes severe headache,
size
vomiting and nuchal rigidity.
• CT / MRI – can identify the site of obstruction; • Causes high output congestive heart failure secondary
diagnose associated Arnold chiari and Dandy walker
to shunting of huge volumes of blood or progressive
malformations.
hydrocephalus and increased intracranial pressure
Differential diagnosis secondary to obstruction of the CSF pathways.
• Megalencephaly
• Chronic subdural hematoma
Treatment 16.4 Posterior Fossa Anomalies
Medical
• Main principle is to reduce the raised intracranial
pressure with mannitol, acetazolamide or diuretics.
16.4.1 Dandy-walker syndrome
All these measures only offer temporary benefit. • Basic pathology is cystic expansion of the fourth
j Acetazolamide at 50 mg/kg/day – reduces CSF ventricle in the posterior fossa and midline cerebellar
production hypoplasia
j Oral glycerol • Primary pathology is the failure of ‘foramen of
Surgical magendie’ to open
• Surgery is considered when head size enlarges rapidly, • Associated with agenesis of the posterior cerebellar
vermis, agenesis of corpus callosum, heterotopia of
or if associated with progressive symptoms.
inferior olivary nuclei, pachygryria of cerebral cortex
• Ventriculo peritoneal shunt is the commonly
and other visceral anomalies.
performed procedure. Shunt enables direct drainage
of CSF into the peritoneal cavity. Rarely ventriculo- • Presents during infancy with rapidly increasing head
size, especially the occiput. Features of long tract
atrial shunting is done
signs, cerebellar ataxia, developmental delay and
• Third ventriculotomy by endoscopic approach
cognitive dysfunction are present.
especially in children with obstructive
hydrocephalus. • Transillumination of the skull may be positive
• Shunt is required for patients with TB meningitis and • Types
Type I- Mega Cisterna Magna
progressive hydrocephalus.
j
Type II- Dandy-Walker variant-Mild enlargement

• Complications of Shunts: Obstruction and Sepsis
j
of 4th ventricle
Prognosis j Type III- Dandy Walker malformation- Massive
• Without appropriate intervention, mortality is very enlargement of 4th ventricle with large posterior fossa.
high. • Managed by the shunting the cystic cavity
• Even treated cases can have varying degrees of
neurological impairment (Seen upto 70% cases).
j Motor defects 16.4.2 Arnold Chiari Malformation
Cognitive impairment – Low IQ, poor memory
• Basic pathology is downward displacement of
j
j Vision problems – Strabismus, Optic atrophy

cerebellar tonsils and brainstem via foramen magnum
j Hearing impairment
causing non-communicating hydrocephalus.
Behavioral disorders
• The term “Chiari malformation” is used to describe
j
all four types of this condition, while the term Arnold

Chiari is reserved for type II
16.3 Vein of Galen Malformation • Types of Chiari Malformation
j Type I
• Results from developmental failure of normal capillary – Displacement of the cerebellar tonsils through
connections between arteries and veins. formen magnum into the cervical canal.
269
mebooksfree.com
– Least severe type and is not associated with Etiology:

hydrocephalus. • Neurological infections - Bacterial meningitis,
– Symptomatic during adolescent or adult intrauterine infections, tuberculous meningitis, aseptic
life. Common presenting symptoms include meningitis, cerebral malaria, tetanus, Reye’s syndrome.
paroxysmal vertigo, drop attacks, vague • Metabolic causes - Dyselectrolytemia (hypocalcemia,
dizziness and headache. Other symptoms hypomagnesemia).
include occipital headache, down gaze • Space occupying lesions - Neoplasm, brain abscess,
nystagmus, periodic nystagmus and oscillopsia. tuberculoma, cysticercosis.
– Associated with other malformations like • Vascular causes - AV malformations, intracranial
syringomyelia and hydromelia thrombosis, and hemorrhage.
j Type II (Arnold Chiari Malformation) • Hypertensive encephalopathy, sequelae of birth
– Occurs due to herniation of inferior vermis, trauma, birth asphyxia, grey matter degeneration,
pons, medulla and elongated 4th ventricle into storage disorders.
the cervical canal • Drugs and poisons - Phenothiazines, salicylate,
– Anomaly of hindbrain due to failure of pontine phenytoin, carbon monoxide, lead.
flexure during embrogenesis. Clinical features of Tonic Clonic Seizures:
– Associated with encephalocele, Progressive
obstructive hydrocephalus and myelomeningocele • Classic form has four phases
j Aura
j Type III
j Tonic
– Herniation of cerebellum into cervical
j Clonic
myelomeingocele
j Postictal phase.
– Associated with hydrocephalus
j Type IV Aura
– Cerebellar agenesis with small posterior fossa • Transitory premonitory symptom.
– There is no herniation or associated hydrocephalus • The child may recognize the impending seizure by the
aura and adopt measures for self-protection.
• Aura may be sensory, visceral, motor and autonomic.
16.5 Seizures Tonic phase
• Lasts for about 30 seconds.
• Definition: A seizure is a brief syndrome of • During this phase skeletal muscles go into a sustained
manifestations resulting from abnormally increased
spasm.
neuronal firing in the brain.
• Shrill cry due to laryngeal muscles spasm.
Types
• Loss of consciousness, pale face, dilated pupils, eyes
• Seizures are broadly classified into are rolled upwards or to the side.
Focal Onset –Involving neurons limited to a
• Frothing from mouth, involuntary passage of urine or
j
particular part in brain

stools.
– Simple partial seizures – Consciousness is
Clonic phase
present during the episode
– Complex partial seizures is associated with loss • Characterized by rhythmic alternating contractions of
of consciousness muscle groups persisting for few minutes.
j Generalized Onset– Universal firing of all neurons Postictal phase
from both hemispheres • Child may complain of headache, confusion,
j Unknown Onset perform autonomic actions, of which he/she has little
• Focal and generalized seizures can be further classified recollection later.
based on motor activity • Transient paresis, loss of bladder/ bowel control may
j Motor Seizures be rarely seen.
– Tonic
– Tonic clonic
– Atonic 16.6 Febrile seizures
– Myoclonic
j Non motor seizures • This term denotes seizures associated with fever due
– Sensory to extracranial source.
– Cognitive • Common neurological disorder in children. Occurs
– Emotional in 3-5% of children below the age of 5 years. This
– Autonomic condition is exclusively seen in children.
j Absence Seizures • Median age of occurrence is between 18–22 months
270
mebooksfree.com
• Occurs in neurologically healthy children. j Age < 18 months

• There should be no evidence of intracranial infection j Complex features
to label as febrile seizures j Uncertain home situation
• These kids have past or family history of febrile seizures. j First episode
Genetics Risk factors for recurrence
• Febrile seizure is a familial disorder. Positive family
history seen in 1/3rd cases Minor criteria Major criteria
• Mode of inheritance is not clear. Autosomal family h/o febrile seizures Age < 1 year
dominant inheritance in some families or epilepsy Seizure within 24 hours
• Febrile Seizure (FS) genes 1 to 10 are identified. FS 1 Complex febrile seizure of fever
gene is located in chromosome 8q13-q21 Daycare Fever 38 - 39° C during
• FS 2 gene is present in chromosome 19p 13.3 and Male sex seizures
codes for sodium channel, SCN1A. Hyponatremia
• The function of other FS genes are not known
Pathogenesis Risk factors for future epilepsy/Seizure disorder
• Exact mechanism not known
• May be an age dependent Minor risk factors Major risk factors
• Response of immature brain to febrile illness Simple febrile seizure Seizure within 1 hour of fever
• Probable etiologies Recurrent febrile Family h/o seizure disorder
j Infections - ASOM, Dysentery, Viral fever etc seizures Focal seizures
j Immunization Impaired neurodevelopment
Types of febrile seizures
• Typical or Simple febrile seizure Investigations
j Age group 6 months to 6 years A) In cases of typical febrile seizures
j Generalized seizure j No neuroimaging or LP required
j Lasting < 15 minutes B) In cases of atypical febrile seizures
j Not recurring within 24 hours j Lumbar puncture
j No post ictal neurological abnormality j EEG if risk or recurrence or future epilepsy
• Atypical or Complex febrile seizure C) To identify the cause of fever
j Age < 5 months or above 6 years j Investigations based on clinical presentation and
j Focal or focal becoming generalized seizure differential diagnosis for fever
j Prolonged > 15 minutes j Hemogram, ESR
j Multiple episodes within 24 hours j Blood, Urine culture
j Associated with postictal neurological abnormality j Serology
• Febrile status Other investigations
Duration of > 30 minutes
• Serum electrolytes, blood glucose, calcium, magnesium
j
One long lasting episode / series of shorter seizures

and blood counts are not routinely needed
j
without regaining consciousness interictally

• Neuroimaging if focal seizures or focal deficits on
• Simple febrile seizure plus examination
Multiple episodes of febrile seizures within 24 hr.
• Indications for lumbar puncture
j
Clinical features j Age < 6 mo

• Seizures are usually generalized tonic – clonic j Toxic and ill appearing child
type. In infants, uprolling of eyes and fixed gaze j Any clinical suspicion of intracranial infection
can be the only feature or may be associated j Age 6 - 12 mo if Hib-2 and pneumococcal vaccination
with tonic movements of limbs. Other types of not done or if status unknown (Relative indication)
seizures like myoclonic jerks, atonic seizures are rare. • Indications for EEG
Though focal seizures can occur, prompt imaging j Family history of epilepsy
should be done to look for focal brain lesions. j Neurological deficit
• Initial clinical examination should be focused at j Developmental delay
j Ruling out meningeal infection
j Identifying the cause of fever Management
j To rule out raised ICT, focal deficits and poor sensorium Immediate management
• Indications for hospitalization • In children with active seizures IV or rectal diazepam
j Lethargy beyond postictal state is the first choice (0.3mg/kg/dose). If facilities for
j Unstable clinical status intubation are available, IV or nasal midazolam
271
mebooksfree.com
• EEG shows characteristic 3 per second spike and slow

wave generalized wave discharge
• Drug of choice- Valproate (previously Ethosuximide)
j Valproate – 15mg/kg initial dose (Maximum
60mg/kg)
j Ethosuximide 20-25mg/kg is used for treatment.
16.8 Status epilepticus
• The clinical manifestations of an abnormal excessive

Figure 16.3 Approach to managing a child with febrile seizures paroxysmal electrical discharge from the brain and
is conducted to the body to produce the seizure
(0.1 -0.2 mg / kg) can be tried. Other options are IV • Status epilepticus is defined as seizures that continue
lorazepam and Rectal clonazepam for more than 30 minutes or recurrent seizures
Long term management for more than 30 minutes without recovery of
• Goal is to prevent recurrence consciousness in between the attacks
• Management options depends on the risk of Incidence
recurrence and epilepsy (Figure 16.3)
• Overall incidence is 50 patients per 100,000
• Continuous daily prophylaxis with antiepileptics or population per year
diazepam is not required in simple febrile seizures.
• Status epilepticus in children is most likely in those
• In cases of parental anxiety, Intermittent diazepam less than3 years of age
prophylaxis can be given during febrile episodes
(Dose - 0.3 mg / kg / dose every 8 – 12 hours if Classification
temperature > 38° C) • Type of seizures
Generalized tonic clonic
• Antipyretic measures and Drug prophylaxis reduces j
but does not completely prevent the recurrence or j Partial

development of seizure disorder j Absence
• Antiepileptic therapy is not required in long term • Clinical presentation
management or prophylaxis against simple febrile j Convulsive type – predominant motor symptoms
seizures (tonic clonic, myoclonic)
j Non-convulsive type – absence, partial or complex
partial
Etiology
16.7 Absence seizures
(Petitmal seizures) Infections Vascular events
• Viral encephalitis • Cerebrovascular
• Pyogenic meningitis accidents
• Characterized by sudden discontinuation of the • Tubercular meningitis • Thrombosis
activity being performed with starring spell, eye • Neurocysticercosis • Embolism
fluttering or rhythmic movements. Metabolic events • Hemorrhage
• The peak prevalence is between 6 and 8 years. • Hypoglycemia Drug intoxication/side
• More common in Girls • Hypocalcemia effects
• Clinical features • Hypomagnesemia Neoplasms
j Sudden cessation of motor activity of speech with a • Hyponatremia Hypoxia/anoxia especially
blank facial expression and flickering of the eyelids during delivery
j No loss of posture, incontinence of urine/stools or Head trauma
breathing difficulty.
j Patients have brief abrupt lapse of awareness or Precipitating factors
consciousness • Febrile illness
j Not associated with Aura or postictal state. • Inadequate antiepileptic drugs (substandard brands/
j No loss of body tone different compositions)
j Automatisms present • Sudden discontinuation of antiepileptic drugs
• Hyperventilation for 3 minutes often precipitates • Sleep deprivation/fatigue/emotional upset
the attacks. Recurrent attacks occurring within a • Central nervous system stimulants like
short time often indicates petit mal status or pyknolepsy. theophylline
272
mebooksfree.com
Pathophysiology Investigations
• Basis of status epilepticus is the failure of mechanism • All cases
that aborts the seizure j Blood biochemistry: Glucose and electrolytes, and
• Failure can be either excessive and persistent other metabolic parameters
excitation or ineffective recruitment of inhibition j Blood gases assessment
• Excitatory neurotransmitters are glutamate, aspartate, • Associated fever
acetylcholine j Blood counts
• Inhibitory neurotransmitters is gamma aminobutyric j Cerebral spinal fluid examination
acid j Urine examination
• Convulsive status epilepticus can be life-threatening j Necessary cultures
and also can cause permanent neuronal damage • Studies on case to case basis
after 1.5–2 hours of seizure activity due to excessive j Electroencephalogram
production of glutamate j Neuroimaging
• This in turn leads to excessive neuronal j Drug levels
depolarization, increase in intracellular sodium and Treatment Protocol
calcium, cerebral edema and finally cell damage and
death • Emergency management focuses on securing the airway,
maintaining oxygenation, ensuring perfusion by obtaining
• Associated features like hypoxia, hypotension, intravenous access and protecting the patient from injury.
acidosis exacerbate neuronal damage
0–5 minutes Observe

Initial observation • Seizure activity; Diagnose SE
and management Airway
• Suction airway
• Supplement oxygen
• Insert nasal airway
Breathing
• Intubate and provide ventilator support if required
Circulation
• Start intravenous line, draw samples for blood sugar and electrolytes
• Glucose may be estimated by a glucometer
• Start two lines if possible
• If hypoglycemic or glycemic status unknown: IV glucose 2 ml/kg
• If age >6 months - 25% glucose, Age <6 months - 10% glucose
Monitoring
• Vital signs monitoring especially pulse oximetry
5–15 minutes • Continue maintaining airway, breathing, circulation and monitoring
Stabilization, • Drug administration
monitoring and IV line established: No IV access:
ABC support Lorazepam 0.1mg/kg (max 5 mg) at 2 mg/min Diazepam rectally 0.5 mg/kg
Drug OR Midazolam intranasal /buccal
administration: Midazolam at 2 mg/min 0.1–0.2 mg/kg 0.2–0.4 mg/kg intramuscular –
First line drugs OR 0.1–0.2 mg/kg
Diazepam 0.2 mg/kg (max – 10 mg) at 5 mg/min Lorazepam sublingual 0.1 mg/kg
Dose can be repeated twice if seizures do not stop Repeat twice if seizures do not stop
within 5 minutes in 5 minutes
Followed by
Fosphenytoin IM—20 mg/kg phe-
nytoin equivalent (PE). Divide in
half and give two separate injections
for more rapid action
15–35 minutes No response, seizures recur or initial seizures more than 10 minutes
Monitoring and Phenytoin (PHT) 20 mg/kg @ 1 mg/kg/min IV infusion (solution only in saline as PHT is
ABC support incompatible with dextrose or calcium)
Drug OR
administration Fosphenytoin (FOS) 20 mg/kg of PE @ 3 mg/kg/min (150 mg/min) (solution in dextrose or
Second line drugs saline) (1.5 mg of FOS = 1 mg of PHT)
273
mebooksfree.com
35–60 minutes • Continue maintaining airway, breathing, circulation and monitoring

(Established SE) • Repeat phenytoin/fosphenytoin 5 mg/kg 2 doses to max dose of 30 mg/kg
Monitoring and • Start third agent—phenobarbitone/midazolam infusion
ABC Support Phenobarbitone 20 mg/kg @ 2 mg/kg/min
Shift to ICU OR
Drug Midazolam drip—0.2 mg/kg IV bolus, followed by infusion of 0.2–2 mg/kg/hour
administration OR
Repeat second line Valproate injection—20 mg/kg bolus over 5 minutes, then maintain at 5 mg/kg/hour for
drug in smaller 6 hours
dose • PLUS
Start third line drug • Give Mannitol infusion to reduce cerebral edema - 5 mL/kg over 10 minutes in all
patients if seizures persist for more than 30 minutes
After 60 More than 60 minutes
minutes(Refractory • Continue maintaining airway, breathing, circulation and monitoring (Ventilator support is
stage) required at this stage)
Monitoring and • Continuous EEG monitoring if available
ABC support • Continuous infusion of midazolam in increasing doses till seizure control
ICU care OR
EEG monitoring Pentobarbital: loading dose: 20 mg/kg over 1 hour followed by a maintenance infusion
Drug administra- of 0.25–5 mg/kg/hour
tion: OR
Induce coma Thiopentone: loading dose: 5–10 mg/kg over 2–5 minutes, maintenance 2–10 mg/kg/hour
OR
Propofol: loading dose 1–3 mg/kg, maintenance 2–10 mg/kg/hour
• Neurological complications include mental j Hamartomas of the iris (Lisch nodules) appear
retardation, focal neurologic deficits, behavioral after 5years
disorders and chronic epilepsy. j Optic gliomas and astrocytomas.
j Hydrocephalus secondary to aqueductal stenosis
j MRI may reveal unidentified bright objects (UBO).
Represents focal areas of dysmyelination with
16.9 Neurocutaneous syndromes increased water content. Not detected by CT scan.
j Congenital glaucoma may occur occasionally.
16.9.1 Neurofibromatosis • Others
j Spontaneous limb fractures (with pseudoarthrosis)
• Two major forms have been described j Macrocephaly, Scoliosis
Neurofibromatosis 1 j Developmental disabilities
• Transmitted as autosomal dominant trait j Attention-deficit hyperactivity disorder.
• NF-1 mutation occur in paternal germline in j Increased risk of malignancies –
chromosome 17 Pheochromocytoma
• Gene NF1 located on 17q11.2 chromosome(codes for j Precocious puberty, Short stature
neurofibromin)
• Commonest presentation is the Diagnostic criteria
• Skin features Neurofibramatosis 1 (von Recklinghausen disease)
j Café-au-lait spots - Present at birth and may
increase in infancy. In prepubertal children, they • Two out of 7 signs is the diagnostic
need to be more than 5 mm in size and at least 6 j ≥ 6 café-au-lait macules; >5mm in great-
in number to suspect neurofibromatosis. est diameter in prepubertal and >15 mm in

j Inguinal freckling (starting in the preschool age) postpubertal individuals
j Axillary or inguinal freckling
and later in the axillae and base of neck.
j ≥ 2 Iris Lisch nodules
j Cutaneous neurofibromas are discrete, soft or firm
j Optic Gliomas
papules, which can occur at any age and at any
j Positive family history
location.
j ≥ 2 neurofibroma or one plexiform neurofibroma
• Eye and CNS features j Skeletal-sphenoid dysplasia or cortical thinning
j Seizure disorder
of long bones ± pseudoarthrosis
j Plexiform neuroma - tumor of nerve and its branches.
274
mebooksfree.com
Neurofibromatosis II
• Central form of neurofibromatosis
• Accounts for 10% of all cases of NF
• Gene on chromosome 22 (Codes for Merlin)
• Hallmark feature of NF-2 is occurrence of Bilateral
eight nerve acoustic neuromas. Presents with tinnitus,
hearing loss.
• Juvenile lens opacifications in 80% cases
• Diagnostic criteria for NF 2
j A parent, sibling or child with NF-2 and either
unilateral eighth nerve masses or any two of the
following
– Neurofibroma
– Meningioma
– Glioma
– Schwannoma
– Juvenile posterior subcapsular lenticular
opacities
16.9.2 Tuberous sclerosis (TSC)

• Bourneville’s disease
• Multisystem disorder transmitted as Autosomal
dominant with variable penetrance.
• Two genes associated with TSC have been
identified
j TSC1 – Located on 9q34 coding for hamartin
j TSC2 – Located on 16p13 coding for tuberin
• TSC is characterised by presence of multiple benign
tumours in various body parts
Clinical features
• May present during infancy with infantile spasms and
a hypsarrhythmic EEG pattern.
• Later may develop into myoclonic epilepsy
• Infantile spasms are treated with vigabatrin
Skin Lesions
• Ash leaf macules
j Hypomelanotic macules seen in 90% cases
j Distributed on the trunk and extremities Figure 16.4 A, Facial angiofibroma. B, Shagreen patch.
j Visualization by the use of a Wood ultraviolet
lamp
j At least three hypomelanotic macules must be • Retinal hamartomas
present. • Depigmented areas
• Adenoma Sebaceum / Angiofibroma (Figure 16.4a) Brain lesion
j Tiny red nodules over the nose and cheeks • Cortical tubers–located in convolution of both
• Shagreen patch (Figure 16.4b) cerebral hemispheres and subependymal region.
j Roughened, raised lesion with an orange peel Number of tubers correlates with the degree of
consistency neurological impairment.
j Located primarily in the lumbosacral region. • Subependymal nodules may calcify and protrude
• Subungual or periungual fibromas into the ventricular cavity, giving rise to the classical
j Arise from the stratum lucidum of the finger and candle-dripping appearance.
toe • Seizure disorder – Most cases present in infancy with
j During adolescence. infantile spasms
Retinal lesions • Intellectual disability and behavioral abnormalities
• Mulberry tumors like autism and ADHA
275
mebooksfree.com
Rhabdomyomas of the heart

• Commonly seen at the left ventricular apex
• Can lead congestive heart failure and arrhythmias
• Resolves spontaneously over a period of time
Angiomyolipomas of kidney
• Benign tumors
• Single or multiple renal cysts are also commonly
present in TS
Lymphangio-leiomyomatosis
• Is the classical pulmonary lesion in TS
• MC in the female patient.
Diagnostic criteria - Tuberous Sclerosis Complex
Major Features Minor Features

• Cortical tuber • Cerebral white
• Subependymal nodule matter migration
• Subependymal giant lines
cell astrocytoma • Multiple dental pits
• Facial angiofibroma or • Gingival fibromas Figure 16.5 Unilateral nevus of face in Sturge Weber
Adenoma sebaceum • Bone cysts syndrome.
• Periungual fibroma • Retinal achromatic
(koenen tumour) patch j Most patients develop seizures during infancy.
• Hypomelanotic macules • Confetti skin lesions Seizures are typically local tonic and contralateral
(>3) • Non-renal to the side of the facial nevus.
• Shagreen patch hamartomas j Other features include slowly progressive
• Multiple retinal • Multiple renal cysts hemiparesis, cortical venous thrombosis, transient
hamartomas • Hamartomatous stroke like episodes and persisting visual defect
• Cardiac rhabdomyoma rectal polyps j Most patients have cognitive impairment and
• Renal angiomyolipoma
severe learning disabilities
• Pulmonary lymphangi-
oleiomyomatosis • Skull radiograph
j Intracranial calcification resembling ‘railroad
Definite TSC is diagnosed when at least 2 major or 1 major plus 2 track’ or ‘tram track’ or ‘Serpentine’ appearance
minor feature are present commonly seen in the occipito-parietal region.
• CT Scan
j Calcification, Unilateral cortical atrophy
Management
• Medical management of Epilepsy
Infantile spasms in TSC respond well to Vigabatrin
j
16.10 Raised intracranial tension
• Refractory epilepsy treated with surgery
• Life threatening condition seen with both traumatic
16.9.3 Sturge-Weber syndrome and non-traumatic neurological illnesses
• Persistent abnormal embryonic vessels leading on to • If not treated as early as possible it may lead to
defective cerebral vascularization. secondary brain injury due to reduced cerebral
• Sporadic disorder perfusion pressure (CPP), and progress into
• Brain becomes atrophic and calcified, especially in herniation syndrome and death
the molecular layer of the cortex. • Intracranial pressure more than 20 mm Hg in
• Clinical manifestations pediatric age group is considered as intracranial
j Presents at birth with unilateral facial nevus hypertension
(Figure 16.5). Upper face and eyelid are always Pathophysiology
involved • In a noncompliant skull vault, intra cranial pressure
j Leptomeningeal angiomas, Buphthalmos and (ICP) is the sum of total pressure exerted by the brain
glaucoma of the ipsilateral eye are seen (≈ 80%), blood (≈ 10%) and CSF (≈ 10%)
276
mebooksfree.com
• The volume of brain tissue increase without a Management

significant change in ICP only if there is an adaptive General measures and first tier therapy
reduction in CSF and cerebral blood volume. When • Head in neutral position, 30° elevation
these mechanisms fail, ICP increases exponentially • Oxygen supplementation to ensure normoxia and
Normal values normocarbia (PaCO2 ~35 mm Hg)
• Intra cranial pressure • Ensure adequate circulating volume
j New born term infants 1.5–6 mm Hg • Maintenance of normal Blood pressure
j Young children 3–7 mm Hg • Osmotic diuretic - mannitol 0.25–0.50 g /kg IV over
j Older children 10–15 mm Hg 20 min, repeat s.o.s.
• Cerebral perfusion pressure OR
j Pressure at which brain is perfused Hypertonic (3%) saline infusion: 10 mL bolus,
j Calculated as the difference between mean arterial 0.1–1.0 mL/kg/hour infusion
pressure (MAP) and intra cranial pressure ICP • Dexamethasone: 1–2 mg/kg IV q6hours - cytotoxic
(CPP = MAP– ICP) cerebral edema (brain abscess, granuloma, tumor)
j Infants/toddlers: more than 40–50 mm Hg and • Cerebrospinal fluid drainage in cases of obstructive
children: more than 50–60 mm Hg hydrocephalus
• Prevent all events that increase intracranial pressure
Etiology like invasive stimuli and loud noise
Increase in brain volume • Antipyretics for Fever
• Cytotoxic edema - Encephalitis, meningitis, head • Adequate sedation–analgesia
injury, Reye’s syndrome • Anticonvulsants for Seizures
• Vasogenic edema - Hypoxic ischemic injury, Second tier therapy
stroke, metabolic encephalopathy • Aggressive hyperventilation (PaCO2 30–35 mm Hg)
• Space-occupying lesions: hematomas, tumors,
• Barbiturates coma: thiopental or pentobarbital
abscesses
• Moderate hypothermia (32–34 °C)
Increase in blood volume
Third tier therapy
• Venous obstruction: Cerebral venous thrombosis
• Vasodilatation: due to hypercapnia, hypoxia or drugs • Decompressive craniectomy or temporal lobectomy
• Status epilepticus • Hyperventilation to PaCO2< 30 mm Hg (use
transiently)
Increase in cerebrospinal fluid volume
• Obstructive or communicating hydrocephalus
• Impaired reabsorption: Hemorrhage into suba-
rachnoid space 16.11 Pseudotumor Cerebri
• Increased production: CSF secreting tumours
• Pseudotumour cerebri (Idiopathic Intracranial
Hypertension)
Clinical features
• In awake patients • This condition is characterized by raised intracranial
pressure without any biochemical or cellular changes
j Irritability, headache and vomiting
in CSF.
j Confusion and decreased alertness
j Neck retraction and tense fontanel on palpation • Though symptoms mimic intracranial space
occupying lesions, it is a benign self-limiting
j Papilledema is usually absent in acute conditions
disorder
• In unconscious/comatose patients
j Raised ICP should be anticipated in head injury, • Characterized by increased intracranial pressure
j ≥ 280 mm Hg in sedated or obese children
meningo-encephalitis, liver disease and diabetic
j ≥ 250 mm Hg in non-obese, non-sedated
ketoacidosis
children.
j Abnormal posturing (decerebration or
decortication) • Normal cerebrospinal fluid (CSF) cell count and
protein content
j Abnormal pupillary dilatation, Papilledema
j Hypertension, bradycardia • Normal to slightly decreased ventricular size,
and normal ventricular anatomy and position
j Irregular breathing, Sixth nerve palsy
documented by MRI.
Investigations • CT Brain is Normal
• Neuroimaging • Papilledema is present in all children with closed
j CT scan plain / contrast fontanelle
j MRI brain – to rule out space occupying lesions • Excessive slow-wave activity on EEG.
277
mebooksfree.com
Etiology • It causes limitation of activity due to a static lesion

Hematologic Nutritional affecting the developing brain
Sickle cell disease Hyperalimentation • The neurological insult can happen during fetal life
Iron deficiency anemia Vitamin A deficiency or during birth or after birth
Aplastic anemia Hypervitaminosis A • Though CP is static disorder, the neurological
Wiskott-Aldrich syndrome Vitamin D-dependent features can change over a period of time. It usually
rickets presents at 2-5 years of life.
Connective tissue disorders Renal • Though CP is predominantly causes motor deficit,
Systemic lupus erythematosus Nephrotic syndrome it can also be associated with sensory disturbances,
Antiphospholipid antibody Chronic kidney disorders of perception, cognition, communication
syndrome disease and behavior. Epilepsy and secondary
Behcet disease Post-renal transplant musculoskeletal problem are also associated with CP.
Misc CNS Etiology
AV malformation, Crohn’s GuillainBarre • Antenatal factors
disease syndrome j Affecting development of brain and is responsible
Obesity (in pubertal patients) Dural sinus for 70-80% cases
Drugs: Tetracyclines, thrombosis • Intrapartum factors
Sulfonamides Head injury j Asphyxia
Nalidixic acid, Steroid Superior vena caval j Exposure to maternal infections
therapy & withdrawal syndrome – Chorioamnionitis
Infections Endocrine – Sepsis
Acute sinusitis Thyroxine therapy – Urinary tract infections
Acute Otitis media Hypo/hyperparathy- – Temperature >38 °C during labor
Mastoiditis / Tonsillilis roidism j Prematurity
Measles, Chicken pox Congenital adrenal j Infants weighing less than 1,000 g
hyperplasia – Last two factors can lead to intraventricular
hemorrhage and periventricular leukomalacia
Clinical Manifestations which can contribute to CP
• Most frequent symptom is headache. Other • Postnatal factors
symptoms include bulging fontanelle, transient visual j Stroke
disturbances. Diplopia (secondary to paralysis of the j Trauma
abducens nerve) is a common feature. j Kernicterus from severe hyperbilirubinemia
• Papilledema with an enlarged blind spot is j Central nervous system infection
consistently seen in older children. j Congenital malformation of brain
• Tangent screen testing reveals inferior nasal defect. Clinical features
• The presence of focal neurologic signs indicates a • Delay in attaining motor developmental milestones
process other than pseudotumor cerebri. • Abnormal muscle tone and reflexes
Treatment • Peristent primitive reflexes like Moro’s, ATNR, Suck,
• Benign Self-limiting condition Rooting etc (Figure 16.6)
• Several lumbar taps and the removal of CSF may offer
symptomatic relief
• Weight reduction for obese children, Restriction of
fluids
• Medical therapy with diuretics like Acetazolamide
(30 to 50 mg/kg/day)
• Ventriculoperitoneal shunt or subtemporal
decompression for severe cases
• Optic nerve sheath fenestration
Complications - Optic atrophy and blindness
16.12 Cerebral palsy
• Cerebral palsy (CP) is a non-progressive Figure 16.6 Persistence of Asymmetric tonic neck reflex
neurological disorder of movement and posture (ATNR) in Cerebral palsy.
278
mebooksfree.com
• Poor coordination Common comorbidities seen in cerebral palsy

• Abnormal movements and postures CNS Eyes Ears
• Delay in speech, visual difficulties, intellectual Variable Squint Deafness
disability degree of Retinopathy of (partial or
• Seizures mental prematurity complete)
• Pseudobulbar palsy and depressed ‘Gag’ reflex leading retardation Cataract Receptive
on to frequent aspirations with feeding Behavioral Coloboma auditory
Classification of cerebral palsy problems Refractive errors aphasia
Based on Motor deficit Seizures Perceptual errors
• Spastic CP (Pyramidal CP) Blindness (partial
j Quadriplegia (20%) -Most severe form of or complete)
CP. It involves all the four extremities with Sensory GIT Miscellaneous
generalized spasticity with mental retardation Spatial disori- Constipation Feeding
and seizures entation Incontinence difficulties
j Diplegia (30%) - Spasticity and weakness Astereognosis Drooling
predominantly involving the lower limbs with Recurrent
minimal or no involvement of upper limbs infections
j Hemiplegia (25%) - It involves either left or right Teeth Speech
side of the extremities. Upper limbs are more Malocclusion Aphasia, Dyslalia
commonly affected at early stage than lower Caries Dysarthria
limbs
j Monoplegia Early diagnosis of Cerebral Palsy:
j Triplegia • Cerebral palsy should be suspected if a child with
• Extrapyramidal CP LBW, perinatal insult has increased tone, feeding
j Choreoathetosis difficulties and does not keep pace with anticipated
j Dystonia normal range of neurological behavior and
• Atonic CP (Cerebellar CP) development.
j Atonic diplegia • Evaluation includes perinatal history, detailed
j Congenital cerebellar ataxia neurological and developmental examination and
• Mixed CP assessment of language and learning disabilities.
Treatment
Based on patient’s status about functional capacity • Treatment of CP involves a multidisciplinary
Class I - No practical limitation approach and team including general pediatrician,
of activity physical and occupational therapists, speech-language
therapist, orthopedist, psychiatrist or neurologist, and
Class II - Slight to moderate limitation
social support services
of activity
• Parent counselling
Class III - Moderate to gross limitation j Should be taught about daily routine activities
of activity like dressing, bathing, eating and follow up by
Class IV - Inability to carry on any useful physiotherapist and occupational therapist
physical activity j Addressing the needs of the patient and the
parents should be done by follow up care center
Diagnosis • Drugs
• History and physical examination with special j Muscle relaxants are used to relieve the
reference to neurological and developmental spasticity - baclofen, dantrolene sodium and
status Benzodiazepines
• MRI or CT of brain to localize the site of lesion or j Hypotonia - strychnine
any congenital malformations j Athetosis - chlordiazepoxide or levodopa,
• Ophthalmic evaluation Dystonia - carbamazepine
• Hearing tests j Epilepsy - anticonvulsants.
• Speech and language evaluation j Botulinum toxin injections along with stretching
• Psychological educational evaluation and/or serial casting to treat joint deformities and
• EEG improves the motor function
279
mebooksfree.com
• Physiotherapy – Soft tissue release to prevent dislocation of hip.

j Most important treatment for CP children – Posterior rhizotomies for spastic diplegia
j Children are trained to relax the spastic muscles Prognosis
by active exercise and establishing the movement • Cerebral palsy is a lifelong disorder
pattern • Children with hemiplegia and diplegia have better
j Physiotherapy involves rhythmic contractions and prognosis than children with quadriplegia
relaxation of muscles and helping the children to
stand and walk on their own
• Surgical procedures 16.13 Mental retardation/
Orthopedic surgery are required to correct the
Intellectual disability
j
deformities and release contractures caused by

spasticity
j Some surgical procedures helpful for CP children • Definition: This term includes a group of children with
are reduced intelligence and learning capacity along with poor
– Tendoachilles lengthening maturation of functions and impaired social adjustment.
– Adductor tenotomy Causes
Prenatal Perinatal Postnatal

A. Genetic: • Birth trauma, A. CNS Infections
• Galactosemia • Birth Asphyxia B. Trauma
• Phenylketonuria • CNS hemorrhage C. Encephalopathy
• Niemann-Pick disease • Prematurity • Hepatic
• Gaucher’s disease • Hypoglycemia • Uremic
B. Chromosomal: • Early onset sepsis • Toxic
• Down syndrome. • Hypothyroidism D. Kernicterus
• Turner syndrome E. Cerebrovascular disease
• Klinefelter syndrome F. Hypothyroidism.
• Fragile X syndrome. G. Metabolic:
C. Intra uterine infections • Hypoglycemia
• STORCH infections • Hypocalcemia
• Chickenpox. • Electrolyte imbalance
D. Maternal factors H. Child Abuse
• Teratogenic Drugs I. Severe Malnutrition
• Radiation exposure
Classification Diagnosis
• Complete History, Anthropometry and Physical
Degree of mental Examination
Intelligence quotient (lQ) retardation • Developmental history and assessment
68 to 83 Borderline • Karyotyping, Ultrasound, Echo Heart, Imaging, Bone
52 to 67 Mild age estimation and metabolic screening in specific
situations
36 to 51 Moderate
• Mental age assessment
20 to 35 Severe j Stanford-Binet scale
Below 20 Profound j Wechsler scale
Treatment
Clinical features • Multidisciplinary approach
• Most cases present with a spectrum of behavioral • Health education, counseling and emotional support
disorders such as hyperactivity, short span of to family members.
attention, distractibility, poor concentration, poor • Occupational and physiotherapy
memory, impulsiveness, clumsy movements, • Basic healthcare, immunization, growth
disturbed sleep, and emotional instability. monitoring.
• Convulsions are common. • Management of associated conditions like seizures,
• Associated defects of musculoskeletal system impaired vision, speech, hearing, musculoskeletal
• Impaired vision, speech and hearing are often found disability, behavioral disorders etc.
280
mebooksfree.com
• Minimal criticism and high appreciation, short Clinical Features:

term goals and structural learning results in less • Onset is usually acute and febrile.
withdrawal, aggressive and hostile reactions. • Symptoms
Prevention j Lethargy and irritability
Headache
• Genetic counseling, vaccination j
Infants presents with Projectile vomiting, shrill cry

• Good antenatal care, good obstetric and postnatal j
supervision to prevent birth asphyxia, injuries, and bulging fontanelle

jaundice and sepsis. j Seizures, altered sensorium progressing to coma
j Photophobia
j Myalgia, arthralgia
16.14 Acute bacterial meningitis/ • Signs
j Tachycardia, cutaneous signs such as petechiae,
pyogenic meningitis macular rashes may be seen.
j Papilledema, hypertension with bradycardia due
• Bacterial disease causing inflammation of meninges to increased ICP
• Associated with high morbidity and mortality. j Generalised hypertonia and neck rigidity
Etiology & Risk factors: j Signs of Meningeal Irritiation
• Common bacterial causes: – Neck stiffness
j Meningococci – Kernig sign – Limited extension of knee beyond
j H.influenzae 135 degrees
j Pneumococci. – Brudzinski sign – Hips and knees flex with
• Age-wise etiology passive neck flexion
j Neonatal Meningitis: E.coli, Pneumococcus, j Focal neurological deficits
Salmonella species, P.aeruginosa & Staph aureus – Hemiparesis
j 3 months – 3 years age: H.influenzae, – Cranial neuropathies are seen usually involving
Pneumococci, Meningococci. nerves II, III, VI, VII, VIII.
j Beyond 3 years to pre-adolescence: Pneumococci, – Hemianopsia
Meningococci. j Tache Cerebrale–Flushing seen with scratching of
• More common in neonates and infants than Abdominal skin
older children because of immature immune system. Presentation in neonates & Young infants
• Patients on immunosuppressive drugs are more • Neck rigidity and kernig sign are not prominent
susceptible to meningitis especially by fungi, listeria • Common presenting symptoms are
and mycoplasma. j Irritability, Refusal to feed & Vomiting
Pathogenesis: j Poor cry, lethargy & Drowsiness
Fever or hypothermia
• Hematogenous spread j
Vacant stare, posturing or clonic seizures

• Head injury can lead to purulent meningitis j
Shock & circulatory collapse

• Extension from contiguous septic foci: Infected paranasal j
sinus, mastoiditis, osteomyelitis, Skull base fracture j Focal neurological deficits

• Recurrent meningitis associated with Meningococcal Meningitis
j Pilonidal sinus • Epidemics caused by Serotype A and C
j CSF rhinorrhea • Sporadic disease by Serotype B
j Traumatic injury to cribriform plate/ethmoidal • Risk factors: Children living in overcrowded houses
sinus • Carrier state is common
j Immunodeficiency disorders • Classical features of Meningitis present
• Leptomeninges infiltrated with inflammatory cells • Pathognomonic finding: Petechial bleeds on the skin
• Cortex of brain shows edema, exudates and and mucosa
profileration of microglia • Specific complication – Waterhouse – Friderichsen
• Basal purulent exduates, especially in inter-peduncular syndrome
and chiasmatic cisterns j Occurs due to hemorrhage and necrosis in the
• Exudates may block Foramens of Luschka & Magendie adrenal gland
resulting in obstructive hydrocephalus j Characterized by
• Thrombophlebitis of cerebral vessels leading to – Adrenal insufficiency
infarction – Hypotension
• Meningococcal meningitis can cause fulminant – Shock
refractory endotoxic shock – Coma.
281
mebooksfree.com
• Chronic Meningococcemia – • Listeria - Ampicillin 300mg/kg/day q6h and

j Intermittent fever, chills, joint pains Aminoglycosides are preferred.
j Chronic maculopapular rashes • Gram Negative Rods – Cefotaxime /Ceftazidime/
Pneumococcal Meningitis Ceftriaxone may be used.
• MC cause of meningitis beyond Neonatal period • Pseudomonas - Combination of Ceftazidime and
• Commonly follows Otitis media, Sinusitis, Aminoglycoside is used. Dexamethasone 0.15mg/kg
Pneumonia or Head injury. i.v. q6h for two to four days is recommended.
• Exudates are common in cortex • Lumbar puncture should not be done in case of
• Sub-dural effusion is a usual complication increased intracranial pressure and osmotic diuresis
with mannitol should be done.
Staphylococcal meningitis
• Anticonvulsants for convulsion.
• In Neonates, often follows umbilical sepsis, • Fluid and Electrolyte imbalance and Hypotension
pyoderma & Septicemia
should be corrected.
• In older children, follows otitis media, mastoiditis,
sinus thrombosis, pneumonia, arthiritis and pyoderma Complications:
Hemophilus influenzae type B meningitis
• Seizures (MC), Increased ICP, cranial nerve palsies,
stroke, SIADH, cerebral or cerebellar herniation and
• Commonly seen in ages 3 – 12 months thrombosis of the dural venous sinuses.
• Sub-dural effusion common ( Suspect in all cases of • Subdural effusions in infants (seen in H.influenza
persisting or secondary fever with focal signs)
and Pneumococcus)
• Convulsions are common • Thrombocytosis, eosinophilia and anemia
• Residual hearing loss is specific common complication • Pericarditis or arthritis
• Vaccine preventable disease • Hydrocephalus, Ventriculitis, Arachnoiditis
• Incidence reduced after the introduction of Hib • MC sequelae of bacterial meningitis - Sensorineural
vaccine
hearing loss
Diagnosis: • Long term neurological complications include
• CSF examination is the cornerstone of diagnosis hemiplegia, aphasia, ocular palsies, sensorineural
j Color – Turbid auditory impairment and mental retardation.
j Elevated cell count
j Microorganisms on gram stain and culture
Neutrophilic leucocytosis (more than > 1000/
j
16.15 Tuberculous meningitis
cu.mm)
j Predominant lymphocytes in partially treated
meningitis • May occur at any age but more common between
j Elevated proteins (above 100 mg/dl) 6 and 24 months of age
j Decreased Glucose concentration (Less than • Caused by M.tuberculosis an aerobic gram-positive
2/3rds of Serum value) bacteria
j CSF culture positive • There is usually a focus of primary infection or
• Blood exam military tuberculosis
j Blood counts raised Pathogenesis
j Blood culture may be positive • Infection reaches meninges by hematogenous route,
• CT scan rarely by lymphatics
• MRI • Has predilection to ‘end arteries’ and cause
‘submeningeal’ tubercular foci
Treatment: • The bacilli is discharged into subarachnoid space
• Based on choice of antibiotic and duration of therapy intermittently leading on to
• Meningococcal or pneumococcal meningitis: j Proliferation
Penicillin 400, 000 - 500,000 units/kg/day every 4th j Perivascular exudation
hourly. j Caseation
• Cefotaxime 150-200 mg/kg/day every 8th hourly. j Gliosis
• Ceftriaxone 100-150 mg/kg/day every 12th hourly. j Giant cell formation
• H.influenzae meningitis: Ceftriaxone / Cefotaxime / • Miliary tuberculosis can also be associated with
Combination of Ampicillin (300mg/kg/day q6h) and tubercles in choroid plexus
Chloramphenicol (100mg/kg/day)
Pathology
• Staph meningitis - Vancomycin is the treatment
of choice if Penicillin or Methicillin resistance is • Meningeal surface and ependyma are inflamed and
covered with grayish yellow exudates and tubercles
suspected.
282
mebooksfree.com
• Changes are mostly seen in at the base of temporal j CSF protein is increased above 40mg/dl and sugar
lobes along middle cerebral artery. usually reduced to about 2/3rd of blood sugar.
• Subarachnoid space and arachnoid villi are Chloride level is less than 600mg/dl.
obliterated resulting in poor drainage of CSF leading • Mantoux test may be positive. If negative does not
to hydrocephalus rule out diagnosis
• Choroid plexus is congested, edematous and contains • Chest X ray may provide supporting evidence of
tubercles pulmonary TB.
• Rarely necrotizing or hemorrhagic • Culture of gastric aspirate and urine.
leukoencephalopathy can occur • CT and MRI show basal exudates and inflammatory
Clinical features: granulomas, hypodense lesions or infarcts and
hydrocephalus.
• Clinical features of untreated case classically goes • BACTEC & PCR
through 3 stages
A) Prodromal stage or Stage of invasion: Differential Diagnosis:
j Insidious onset with low grade fever • Purulent meningitis
j Irritability and restlessness • Partially treated purulent meningitis
j Loss of appetite and disturbed sleep • Encephalitis
j Vomiting and headache • Typhoid encephalopathy
j Child may exhibit head banging and photophobia • Brain abscess
B) Stage of meningitis: • Brain tumor
j Neck rigidity and kerning sign positive. • Chronic subdural hematoma
j Remittent or intermittent Fever • Enteric encephalopathy
j Disturbed breathing Treatment:
j Child is drowsy or delirious • Antitubercular therapy - should be prompt, adequate
j Convulsions and focal neurological deficit like and prolonged for at least 12 months.
monoplegia and hemiplegia may occur. • At least 4 anti-tubercular drugs should be used for
j Sphincter control is usually lost. initial 2 months comprising
C) Stage of coma: j Isoniazid( 5mg/kg/day, max 300 mg )
j Loss of consciousness, rise of temperature and j Rifampicin(10mg/kg orally,max 600 mg)
altered respiratory pattern. j Ethambutol(15-20 mg/kg/day)
j Dilated pupils, nystagmus and squint j Pyrazinamide (30mg/kg/day orally)
j Ptosis and ophthalmoplegia j Streptomycin (30-40 mg/kg/day)
j Cheyne-stokes / Biot’s breathing • Steroids - parenteral dexamethasone 0.15mg/kg,
j Bradycardia every 6 hrIV, Change to oral prednisolone once brain
j If untreated, is lethal in 4 weeks edema settles.
Complications: • Steroids reduce the intensity of cerebral edema, risk
of development of arachnoiditis, fibrosis and spinal
• Hydrocephalus is one of the common complications block.
j Other potential complications include:
• Stroke • Symptomatic therapy of raised intracranial pressure,
seizures, dyselectrolytemia should be done.
• Epilepsy
• Tuberculoma • The patient should be kept under observation for
papilloedema, optic atrophy or increased head
• Cranial Nerve palsies circumference.
• Myeloradiculopathy
• Hypothalamic syndrome • Ventriculocaval shunt may be required for increasing
hydrocephalus and persistent decerebration.
• Iatrogenic complications like hepatotoxicity due to
anti-tuberculous medications.
Diagnosis:
• High clinical suspicion 16.16 Viral meningoencephalitis
• Lumbar puncture–CSF examination
j CSF pressure is elevated to 30-40 cm water. Clinical features
j May be clear and colorless • The initial symptoms are high fever, mental
j On standing, cob-web formation occurs due to confusion, headache, vomiting, irritability, apathy or
bacilli enmeshed in fibrin loss of consciousness often associated with seizures.
j CSF reveals increased cells 100-400/cu.mm, • Decerebration, cardiorespiratory insufficiency,
polymorphic nuclear cells may predominate in hyperventilation and autonomic dysfunction due to
early stages but are replaced by lymphocytes. raised intracranial pressure.
283
mebooksfree.com
• Extrapyramidal symptoms are common in Japanese B • Others

encephalitis. j Penetrating headinjuries
• Lateralization to one side with Temporal or Frontal j Immunodeficiency states
involvement is common in herpes encephalitis. j Infection of ventriculo-peritoneal shunts.
• Typical features like increased intracranial pressure Pathology
and papilledema and evidence of brainstem
• Most cases occur in frontal, parietal, and temporal
dysfunction. lobes (80%). Occipital lobe, cerebellum, and
• Herniation of cerebellum through the foramen brainstem accounts for the remaining 20% cases.
magnum causes distortion and compression of
• Cerebral abscesses are evenly distributed in both
medulla oblongata with severe disturbances of vital hemispheres
centers leading to respiratory or cardiac arrest.
• An abscess in the frontal lobe is often caused by
• Unchecked brain swelling may lead to herniation extension from sinusitis or orbital cellulitis, whereas
at tentorial hiatus, compression of midbrain abscesses located in the temporal lobe or cerebellum
causing deterioration in consciousness, are frequently associated with chronic otitis media
pupillary abnormalities, ptosis, 6th nerve palsy, and mastoiditis.
ophthalmoplegia, paralysis of upward gaze
• Abscesses occurring due to penetrating injuries are
Virus specific symptoms in Encephalitis single and often caused by Staph aureus
• HSV encephalitis Etiology
Involve temporal lobe and orbital portion of
• Aerobic and anaerobic streptococci (Most common
j
frontal lobe
causes)
Focal findings on EEG
• Other Anaerobic bacteria (Bacteroides,
j
j High protein concentration in CSF

Fusobacterium, Prevotella, Actinomyces) spp.
Drug of choice is Acyclovir
• Streptococcus aureus, Pneumococcus, H. influenzae
j
• Mumps • Enterobactericiae - Proteus,Klebsiella.

Meningo encephalitis
• Citrobacter commonly causes neonatal brain abscess
j
Hypoglycorrhachia is common (less glucose)

• Fungi, Nocardia, Mycobacterium,and Listeria in
j
j Damage to 8th cranial nerve is important

immunocompromised children
sequelae
• Varicella-Zoster virus Clinical features
j May cause CNS infection in close temporal • Early nonspecific symptoms like Fever, bodyache,
relationship with chickenpox. headache, vomiting and lethargy. As disease
j Manifestations include cerebellar ataxia, acute progresses, seizures, papilledema, focal neurologic
encephalitis. deficit and poor sensorium ensures.
• Human herpes virus 6: Cause encephalitis, especially • Cerebellar abscess presents with nystagmus, ipsilateral
among immunocompromised hosts. ataxia and dysmetria, vomiting, and headache.
• Rupture of abscess into ventricles can lead to
profound shock and immediate death.
Diagnosis
16.17 Brain abscess • Hemogram, peripheral smear
• Blood culture – positive in 10% cases
• Brain abscesses is commonly occurs in two pediatric • Pus culture
age groups • CSF Analysis
j Between 4 and 8 yr old j Variable results
j In neonates j Minimally elevated WBCs and protein
Risk factors
• EEG– focal slowing
• Radionuclide brain scan - ‘area of enhancement’ due
• Cyanotic congenital heart disease with right-to-left to disrupted Blood brain barrier
shunts (eg: tetralogy of Fallot),
• CT with contrast – Ring enhancing lesion
• Direct extension from • MRI – Diagnostic test of choice. Reveals increased
j Meningitis
signal intensity in T2-weighted images
j Chronic otitis media, Mastoiditis, Sinusitis
j Soft-tissue infection of the face or scalp Treatment
j Orbital cellulitis, Dental infections Medical
• Hematogeneous spread • For empirical management, combination of
j Endocarditis third-generation cephalosporin, vancomycin and
j Pneumonia metronidazole is used
284
mebooksfree.com
• Duration of antibiotic therapy 4 – 6 weeks. • The disorder is generally self-limited and lasts from a
• Indications for medical therapy few weeks to months.
j <2 cm in diameter • Child should be protected from injury, bedding
j Short duration of illness (<2 wk) should be well padded.
j No signs of Raised ICT • Drugs like chlorpromazine, haloperidol, sodium
j No neurological impairment valproate or carbamazepine may be used
Surgical • Aspirin/Steroids help to limit the course of chorea.
• Open surgical drainage • Anti streptococcal prophylaxis with Penicillin
• Indications for Surgery G should be given to prevent the recurrence of
j >2.5 cm in diameter rheumatic activity
j Presence of gas
j Multiloculated abscess
j Posterior fossa abscess 16.20 Disorders of neuromuscular
Fungal etiology
system
j
Prognosis
• With adequate treatment overall prognosis is good.
• Mortality is <5% 16.20.1 Guillian-barre syndrome
• Poor prognostic factors
j Age: Infancy
• Post infectious polyneuritis
j Multiple abscess
• Two third patients have history of viral infection
preceding the illness
j Neurological deficit
j Poor sensorium
• Neurologic manifestations begins 2-4 weeks after
viral infection
• Seizures, focal deficits, hydrocephalus, behavioral and
learning problems can be seen in surviving children. Etiology
• Campylobacter infection associated with severe forms
and acute motor axonal neuropathy (AMAN) syndrome
• Common viral illness causing GBS are
16.18 Subacute sclerosing j Infectious mononucleosis
pan-encephalitis j Mumps
j Measles
• Other viruses like echo, coxsackie and influenza virus
• This condition follows several months to years after • GBS can follow rabies infection or administration of
an attack of measles. neural vaccines for rabies
• Age of onset is 5–15 years.
Clinical features
• Minor personality changes may be observed
• School performance deteriorates in early stages. • Pain in the muscles is early symptom
• Later slow myoclonic jerks in the trunk and limbs • Weakness starting in legs then spreading to upper
are observed. extremities and trunk muscles (Ascending type of palsy)
• Progressive neurologic deterioration occurs. • Weakness is more marked in proximal muscles
• EEG shows characteristic periodic slow waves with • Tendon reflexes are diminished, plantar is normal
high voltage and burst suppression pattern. with hypotonia
• Cranial nerve involvement seen in three fourth cases
• Sensory symptoms are subjective rather than
objective
16.19 Sydenham’s chorea • Autonomic nervous system involvement
j Urinary retention
j Hypertension
• More common in girls than boys. j Postural hypotension
• Irregular, nonrepetitive, quasi purposive and • Respiratory insufficiency due to paralysis of
involuntary.
intercostal muscles
• Movements are aggravated by attention, stress or
excitement Investigations
• Movements disappear during sleep. • CSF analysis shows albumino cytological dissociation
• When hand is outstretched above the head, forearm • Protein are elevated > 45mg/dl
tends to pronate. Differential diagnosis
• Milkmaid’s grip and darting tongue is seen. • Poliomyelitis
• Audible click is heard during speech. • Polymyositis
285
mebooksfree.com
• Transverse myelitis • Episodic apnea is present

• Heavy metal intoxication • Myasthenia crisis is absent
Treatment • No risk of developing myasthenia gravis in later
• Self-limiting with gradual recovery in 6 months – 2 years childhood
• Intravenous immunoglobulin 300 – 400 mg/kg for Post-infectious myasthenia gravis – usually follows vari-
5 days cella-zoster infection in 2-5 weeks as an immune response.
• Plasmapheresis • Myasthenia gravis is occasionally associated with
• Physiotherapy is mainstay to prevent handicaps hypothyroidism, usually due to Hashimoto’s thyroiditis
• Thymomas rarely coexist with myasthenia gravis
in children (<5%), which produce unique form of
16.20.2 Myasthenia Gravis myasthenia in adults called Eaton-Lambert syndrome.
• Neuromuscular junction disorder characterized by Laboratory Findings:
waxing-waning course and easy fatigability which • EMG is more specific than a muscle biopsy.-A
improves after rest. decremental response is seen to repetitive nerve
• In infants and children, the spectrum of myasthenia stimulation. The muscle potentials diminish rapidly
gravis (MG) includes in amplitude until the muscle becomes refractory
j Juvenile myasthenia gravis to further stimulation. Motor nerve conduction
j Transient neonatal myasthenia velocity remains normal. The unique EMG pattern
j Congenital myasthenia is electrophysiologic correlate of the fatigable
Juvenile Myasthenia Gravis: weakness observed clinically and is reversed after a
• Slowly progressive course with relapsing-remitting cholinesterase inhibitor is administered.
tendency with variable or fatigable weakness • Anti-Ach antibodies is demonstrated
• Difficulty in chewing or swallowing, fatigability or • Edrophonium test- short acting cholinesterase
hoarse voice, diplopia especially on sustained gaze inhibitor is given and looked for relief of symptoms.
or continuous activity like reading, weakness of jaw, • For infants- neostigmine is given.
orthopnea secondary to diaphragmatic weakness; Treatment:
limb girdle weakness • Aimed at inducing and maintaining complete clinical
• Eye signs: Ptosis is the earliest sign; Peep sign- on or pharmacological remission with minimal adverse
attempting to tightly close the eyes, after few minutes, effects
the cornea may get exposed due to inability to sustain • Mild myasthenia requires no treatment.
contraction of orbicularis oculi, ophthalmoparesis. • Neostigmine methylsulfate (0.04mg/kg) may be
Pupillary responses to light are preserved given intramuscularly every 4-6 hours
• Facial weakness: compensatory wrinkling of forehead • Steroid treatment is effective
(due to hypercontracted frontalis to maintain eye • Steroid sparing agents (Azathioprine)
opening), expressionless facies, Snarl on trying to • Thymectomy is done in high titers of anti-Ach
smile; inability to close the jaw receptor antibodies (but ineffective in congenital and
• Other cranial musculature: Bulbar weakness, tongue familial forms of myasthenia gravis)
may show triple longitudinal furrowing • Rituximab, a monoclonal antibody to the B-cell
• Skeletal musculature: proximal limb weakness, CD20 antigen.
tachypnea/shallow respiration • Transient maternally transmitted myasthenia gravis
• Tendon stretch reflexes may be diminished and rarely lost require cholinesterase inhibitors for only a few days.
Transient neonatal myasthenia gravis: • Chronic therapy
• Occurs due to transplacental transfer of maternal j Immuno-modulatory treatment: Steroids,
acetylcholine receptor blocking antibodies Monoclonal antibodies, thymectomy
• Neonates present with inability to suck or swallow, j Acetylcholinesterase inhibitor – Pyridostigmine
generalized hypotonia, weakness and respiratory • Treatment of Acute exacerbations
insufficiency. Symptoms improve within a week and j Short-term immunotherapy: I.V. immunoglobulin
completely resolve by 4 weeks 2g/kg over 2–5 days, Plasmapheresis
• Risk of developing myasthenia gravis in later
childhood is not increased 16.20.3 Infant Botulism
Congenital myasthenic syndromes • Disorder of neuromuscular junction
• Autosomal recessive • Results from ingestion of food contaminated with
• Weakness of extra ocular, pharyngeal and respiratory Clostridium botulinum neurotoxin. Honey is the
muscles common source
286
mebooksfree.com
• Short Incubation period (few hours) • Anal and urethral sphincter weakness can lead to
• Initial symptoms are non-specific and include nausea, Incontinence.
vomiting, lethargy and diarrhea. • Ankle deep tendon reflexes remain well preserved
• Symptoms due to cranial nerve involvement- until terminal stages.
Diplopia, dysphagia, weak suck, facial weakness, and • Some cases present during infancy itself with poor
absent gag reflex. head control and hypotonia.
• Symptoms rapidly progress to flaccid paralysis and • Sudden episodes of vomiting, abdominal pain and
respiratory failure distension due to Acute gastric dilation (intestinal
• No specific antibody available. Guanidine may be pseudo obstruction)
effective for extraocular and limb muscle weakness Complications:
but not for respiratory muscle involvement.
• Pulmonary infection and respiratory insufficiency
(Most common cause of death)
16.20.4 Duchenne Muscular • Rapidly progressive Scoliosis
Dystrophy • Cardiomyopathy and congenital heart failure
• Cognitive impairment
• Most common form of hereditary neuromuscular
disease characterized by progressive muscle weakness
• Seizure disorder
• Transmitted as X-linked recessive trait Laboratory findings:
• Cases present before 5 years of life • Serum CPK levels are markedly elevated.
Pathogenesis
• A normal CPK level is incompatible with the
diagnosis of DMD. In terminal stages CPK levels
• Basic pathology involves mutation in dystrophin gene reduce because of less muscle mass to degenerate.
located on the short arm of X chromosome in the
Xp21 region.
• Serum Aldolase and aspartate aminotransferase levels
are increased
• Dystrophin is a large cytoskeletal protein bound to
sarcolemma, providing structural integrity to muscle
• ECG: Tall right precordial R waves; deep Q waves in
limb or left precordial leads
membrane.
• Carrier screening - Detection of female carriers by
• Approximately 30% of cases of DMD are due to new serum CPK estimation or quantitative EMG and
mutations without the mother being a carrier
genetic counseling based on localization of the gene
• Large size of the gene is responsible for such using DNA polymorphism
high mutation. Large deletions or duplications in the
gene account for about 70 percent of cases of DMD. Diagnosis:
• Rarely females can be affected due to X-chromosome • EMG: Reduced amplitude and duration of motor unit
inactivation (Lyon’s hypothesis) and in Turner’s potentials.
syndrome (45 XO Karytype) • Muscle biopsy is diagnostic (Vastus lateralis and
Clinical Features: gastrocnemius muscles are preferred)
• Typical cases present before 5 years of age with • Blood PCR for dystrophin gene mutation
difficulty in standing, walking and climbing stairs due • Multiplex PCR is more sensitive. Multiplex
to weakness of pelvic girdle muscles. ligation-dependent probe amplification (MLPA) are
• Pseudohypertrophy (muscle is replaced by fat and commonly employed genetic techniques.
connective tissue) and wasting of thigh muscles. Treatment:
Pseudohypertrophy is characteristically seen in calf • No effective treatment available till date. Most cases
muscles followed by tongue, glutei, deltoid and are fatal by second decade of life.
brachioradialis. • Short course of steroids are known to slow the
• Gower’s sign - climbing up one’s own thighs while disease progression –Prednisolone (0.75mg/kg/
attempting to rise from ‘sitting of floor’ position due day) - decrease the rate of apoptosis of myotubes
to pelvic girdle involvement during ontogenesis. Deflazacort- 0.9mg/kg/day
• Waddling gait (Trendelenburg gait) may be present. is equally effective. Fluorinated steroids such as
• Valley sign- hypertrophy of deltoid and infraspinatus dexamethasone, induce myopathy by altering the
with wasting of posterior axillar fold muscles. myotube abundance of ceramide
• Proximal muscles and neck flexors are particularly • Physiotherapy – Effective stretching and appropriate
involved more and function of the distal muscles are positioning at various joints
relatively preserved. • Contractures - Prevention with assistive devices,
• Contractures involving the ankle, knees, hip and treatment with surgery
elbows. Muscles like supraspinatus and sternal head • Exon skipping, gene therapy, cell therapy, novel
of pectorialis major are often atrophied. pharmacological approaches (utrophin upregulation,
287
mebooksfree.com
myostatin inhibitors) are being studied. Drisapersen

and eteplirsen are axon skipping antisense
oligonucleotides under development
Prognosis
• All cases become bedridden by 12 years of age.
About 90% cases die before 20 years usually from
cardiomyopathy or pulmonary disease.
16.20.5 Bell’s palsy

• This condition is an acute onset, unilateral, LMN
type of seventh cranial nerve palsy that often follows
certain viral infections
• This facial palsy is an isolated finding and usually
there is no other associated cranial nerve palsy or
neurological deficit.
• Common pediatric disorder
• Onset is usually sudden and occurs approximately
2 weeks after a viral infection
Etiology
Figure 16.7 Bell’s palsy.
Infectious causes Non-infectious causes
• Epstein-Barr virus – • Interferon alpha
Most common therapy
• Diffusion tensor tractography – 3D modelling
• Varicella-zoster virus • Ribavirin therapy technique to visually map neuronal tracts
(Chicken pox, Herpes • Type 1 diabetes
Zoster) mellitus
• Ultrasound of Facial nerve
• Herpes simplex virus • Hypertension Treatment
• Mumps virus • Trauma • Supportive treatment
• Lyme disease • Tumour j Eye care – Lubrication and Eye patch to prevent
• HIV infection exposure keratitis
• Rickettsia, Mycoplasma j Physiotherapy
infections • Steroids
j First line therapy
Clinical features j Started within 7 days of symptoms
• Characterized by unilateral involvement of both j Associated with excellent outcome.
upper and lower half of face (Figure 16.7) j Oral prednisolone is preferred (Dose of 1-2 mg/
• Findings on affected side kg/day for 7 days).
j Difficulty in closing eyes. Can lead to exposure • Experts also routinely recommend a course of
keratitis antiviral therapy. Oral acyclovir or valacyclovir is
j Loss of forehead wrinkling commonly used.
j Loss of taste on anterior 2/3rds of the tongue • Surgical decompression
• Findings on contralateral side • Laser therapy
j Deviation of angle of mouth (exaggerated while Prognosis
laughing, crying etc) • Most cases (>85%) recover spontaneously and
j Drooping of the corner of the mouth completely. In chronic cases with residual weakness,
• Bell’s phenomenon (Palpebral oculoyric reflex)– physiotherapy, surgery or laser therapy can be tried.
Upward and outward movement of eyeball when eyes
are closed.
Diagnosis Online supplementary materials:
• Clinical diagnosis Please visit MedEnact to access chapter wise MCQs and
• MRI – To study the facial nerve anatomy and previous year pediatrics theory questions asked in various
associated lesions final MBBS University examinations.
288
mebooksfree.com
Chapter | 17 |
Endocrinology
Clinical features
17.1 Growth hormone deficiency • These children have normal growth at birth since
(GHD) GH plays very minor role in fetal growth. Growth
retardation usually manifests at around 1 year of age.
Length / Height is usually <3rd percentile for the age and
Physiology
the height velocity is reduced to as low as 1 cm/year.
• Somatotropes in the anterior pituitary are However, normal body proportions are maintained
responsible for synthesis, storage and secretion of
(Proportionate short stature) throughout the course.
growth hormone (GH). GH is secreted in pulsatile
fashion and not continuous.
• Classic description includes a very short and plump
child with immature facies, prominent forehead
• Sleep, exercise, physical stress, ghrelin, fasting and and midline facial abnormalities (Cleft palate, cleft
hypoglycemia stimulate the secretion of GH while
lip, Single central upper incisor teeth, prominent
hyperglycemia, steroids and stomatostatin inhibits its
philtrum). Eyes appear very prominent with depressed
secretion.
nasal bridge/saddle shaped nose. Micrognathia,
• Functions of GH includes increase in the linear crowding of teeth, nystagmus with impaired vision and
growth, bone thickness, soft tissue growth, protein
a high pitched voice are other features. Hands and feet
synthesis and release of fatty acid from adipose
are relatively small with slowly growing nails and hair
tissue
• Bone age and eruption of teeth are delayed.
Etiology • Gonadotropin deficiency can lead to hypogonadism
• Congenital and small sized genitalia (micropenis) in boys
j Isolated GH deficiency • Mental development and intelligence are normal
j Multiple or complete deficiency of pituitary • Regular height monitoring helps in early detection
hormones • Cases can present occasionally with hypoglycemia
j GH releasing hormone deficiency & prolonged jaundice in the neonatal period due to
j Developmental defects associated ACTH deficiency.
j Pituitary aplasia/hypoplasia • Evaluation- History, examination and investigation
j Anencephaly
j Holoprosencephaly Growth related • Infants and children with
• Acquired history GHD have growth failure
j Tumors: Pituitary, Hypothalamus Patient physical • Short stature and growth
j CNS Infiltration: Histiocytosis, Hemochromatosis, examination failure may be the only
sarcoidosis clinical feature present
j Injury: Post-surgical, Perinatal asphyxia, head Imaging and other • Diagnosis is based on
injury evaluations clinical, Auxology &
j Vascular: Aneurysm, infarction biochemical parameters
j Cranial Irradiation • Bone age assessment
j CNS Infections • MRI/CT Brain
289
mebooksfree.com
Laboratory • Measurement of GH, IGF1, j Vasopressin insensitive DI or Nephrogenic DI

evaluation IGF1 binding protein levels –due to deficient renal sensitivity to ADH leading
• Determination of peak GH to passage of dilute urine inspite of adequate ADH
levels after stimulation test production
• Insulin, Clonidine, L-dopa, Physiology
Arginine, Glucagon, GnRH
are used for stimulation
• Factors stimulating ADH release from posterior
pituitary are increased serum osmolality and severe
Special testing • Family history and genetic volume depletion.
testing • Urine concentrating ability of kidney is dependent on
three critical factors
• Children with height below third centile and height j Urine delivery to collecting tubule
gain less than 4 cm/year over a period of observation j Intact concentrating gradient in renal medulla
for at least 6 months, with a bone age below the j ADH dependent regulation of water permeability
chronologic age needs evaluation for GHD in the collecting tubule
Treatment • ADH acts via Aquaporin 2 (AQP-2) channel which
• Early diagnosis followed by prompt intervention with is a cAMP mediated water channel, present in the
exogenous GH helps in achieving maximum target luminal membrane of the collecting duct. ADH binds
height. to AVPr2 receptor on the tubular cell leading to AQP-
• Recombinant hGH dose of 0.23-0.3 mg/Kg/week 2 activation. This leads to
(1 mg = 3 IU) subcutaneously till adequate growth is j Increase in sodium absorption in ascending loop
achieved of henle
j Catch up growth occurs during first 2-3 years of j Increased water permeability of DCT and
treatment collecting duct resulting in increased water
j Treated children gain 10 -12 cm of height within reabsorption and concentrated urine
first year and 6-8 cm/yr thereafter • Nephrogenic DI is due to failure of the renal tubules
j With GH therapy, response typically declines over to respond to vasopressin defects in the AQP2 and
years followed by normal pattern of growth AVPr2 genes result in.
• Indications for stopping GH therapy
j Height gained per year reduced to 1 cm Etiology
j Current height close to target height
j Bone age over 16 years in boys and 14 years in Cranial/Central DI Nephrogenic DI
girls • Meningitis • Hypercalcemia
• Complication of GH therapy: Increased risk of • Severe head injury • Hypokalemia
j Slipped capital femoral epiphysis, pseudo tumor • Brain tumor • Drugs: Lithium,
cerebri, worsening of scoliosis • Post-pituitary surgery Demeclocycline
j Impaired glucose tolerance test. • Brain secondaries • Tubulo interstitial disease
j Reversible hypothyroidism. • Stroke • Obstruction\
pyelonephritis
Clinical features:
17.2 Diabetes insipidus (DI)
• Cases typically present with massive polyuria, volume
depletion, hypernatremia, hyperthermia and crying
• DI is disorder of water metabolism due to deficient episodes. Constipation and poor weight gain are also
secretion or action of Anti-diuretic hormone (ADH) seen
• DI is characterized by an inability to concentrate • After multiple episodes of hypernatremia, patients
urine may develop developmental delay and mental
• ADH is secreted from supraoptic and paraventricular retardation
nuclei of hypothalamus, transported via axons and • Diminished appetite and poor food intake because of
stored in the posterior pituitary the need to consume large volume of water during the
• Some cases show X linked recessive pattern of daytime
inheritance
• Two types of DI: Evaluation:
j Vasopressin sensitive DI or Cranial DI or Central • The diagnosis is suggested in a male infant with
DI – due to deficiency of antidiuretic hormone polyuria, hypernatremia, and diluted urine
(ADH), leading to loss of excessive water due to • Polyuria – 24 hour urine output > 4 litres
passage of dilute urine • Dilute urine – Urine specific gravity – 1.001 – 1.005
290
mebooksfree.com
Endocrinology Chapter | 17 |
• A 3 hour water deprivation test increases plasma j Type 1 DM: Insulin deficiency because of
osmolality. pancreatic β cell damage, most common
• Nephrogenic DI: Administration of vasopressin j Type 2 DM: Insulin resistance occurring at the
(10-20 µg intranasally) followed by serial urine and level of skeletal muscle, liver and adipose tissues.
serum osmolality measurements hourly for 4 hr Type 1 Diabetes Mellitus
confirms poor response to ADH Etiology and pathogenesis
• Radioimmunoassay reveals reduced serum ADH • It is a chronic autoimmune disease involving the beta
levels(< 0.5 pg/ml) cells of pancreas that secretes insulin
Treatment • Characterized by gradual loss of insulin secretion
• Central Diabetes insipidus resulting in hyperglycemia
j Treatment of underlying cause • Genetics: Major susceptible loci are
j Desmopressin (DDAVP) a synthetic analogue of j HLA class II gene
ADH vasopressin-tablets or nasal spray j Insulin gene
j Some patients respond to Chlorpropamide since it j Cytotoxic T lymphocyte antigen 4
potentiates the action of ADH j Protein tyrosine phosphatase N22 gene
• Nephrogenic Diabetes insipidus • Environmental factors:
j Adequate fluid intake should be maintained j Autoimmunity by molecular mimicry or by
j Restricted sodium intake in older patients directly stimulating cytokine production
(<0.7 mEq/Kg/24 hr) j Viruses implicated in etiology are
j Diuretics – Coxsackie
– Thiazide diuretics - 2-3 mg/kg/24 hr – Enteroviruses
– Potassium sparing diuretics (amiloride) – Mumps
0.3 mg/kg/24 hr in three divided doses – Congenital rubella infection
j Indomethacin (2 mg/kg/24 hr) can be tried in j Early weaning to cow’s milk and exposure to gluten
those who respond poorly to diuretics. • DM is frequently associated with other autoimmune
diseases like Hashimoto thyroiditis, pernicious
anemia and Addison disease
Pathophysiology:
17.3 Diabetes mellitus (DM) • Insulin mainly acts on three tissues Liver, muscle and
adipose tissue
• It is a common, chronic, metabolic disease • Concomitant rise in the counter regulatory hormones
characterized by hyperglycemia as a cardinal like glucagon, epinephrine, cortisol and growth
biochemical feature. hormone results in hyperglycemia and ketogenesis
• The major forms of Diabetes are (Figure 17.1)
Figure 17.1 Pathophysiology of Type 1 Diabetes Mellitus and DKA.
291
mebooksfree.com
Functions of Insulin j Two-hour plasma glucose ≥ 200 mg/dL during

Liver Induces oral glucose tolerance test on two occasions
• Glucose uptake (glucose load 1.75 gm/kg) (or)
• Glycogen synthesis j HbA1c > 6.5%
• Lipogenesis Management
• Inhibits gluconeogenesis • Principles of managing type 1 Diabetes mellitus
Muscle • Glucose uptake and oxidation includes
• Glycogen synthesis j Treatment of diabetes in hospital and home
Adipose Tissue • Glucose uptake management
• Lipid synthesis j DKA treatment in hospital
j Post acidosis therapy in hospital and discharge
• Blood sugar exceeding the renal threshold of planning
180 mg/dl leads to A) Management of newly diagnosed case
j Glycosuria j Any newly diagnosed case should be admitted in
j Diuresis hospital for initial stabilization.
j Electrolyte loss j Objectives of management include
j Dehydration – Confirmation of diagnosis
j Hyperosmolarity – Control of hyperglycemia
• Untreated dehydration and acidosis cause cerebral – Titration of medications and identifying
obtundation and circulatory failure optimal dose
Clinical Features – Treatment of infections, dehydration or any co-
morbid disease
Typical features • Polyuria
– Treatment and prevention of Diabetic
• Polydipsia
• Polyphagia ketoacidosis
• Weight loss – Screening for complications and prevention
• Weakness – Ensuring adequate nutrition for optimal growth
and development
Ketosis • Vomiting
• Dehydration Subcutaneous Insulin therapy
• Abdominal pain j In most cases, euglycemia is achieved with a dose
• Kussmaul respiration of 0.5 unit/kg/day
• Fruity odor of acetone in j Insulin requirement is 60% of total replacement
breath dose in new cases as β cells retain some residual
Ketoacidosis • May mimic abdominal surgical function (Honeymoon phase).
emergency j Two thirds of total dose is given 30 minutes before
Severe acidosis • Decreased consciousness and breakfast and one-third dose 30 minutes before
hypotension dinner. Each dose consists of 2/3rd lente (NPH)
• Fever – important clue to infection and 1/3rd regular insulin (Split-mix regimen - Mix
of regular & intermediate acting insulin).
Laboratory Investigation j Addition of plain insulin at lunch time is useful
for better control of sugars
Diabetes Mellitus DKA j Preferred sites are back of upper arm, front of
• Glycosuria • Blood pH below 7.3 thigh, abdomen and buttocks.
• Hyperglycemia • Bicarbonate below j Site of injection must be changed each time to
• Ketonemia 15 meq/L avoid lipodystrophy
• Ketonuria • Increased anion gap j Other insulin delivering systems:
• Hypertriglyceridemia - >10 mmol/L – Insulin pump therapy
typical • Normal serum sodium – Continuous glucose monitoring systems
• Leucocytosis may • Normal or raised – Amylin based adjunct therapy
be present without potassium B) Management of Diabetic Keto Acidosis
infection • Serum ketone positive j DKA is a life threatening emergency.
j Principles of DKA management
Diagnostic criteria for diabetes mellitus – Immediate restoration of fluid volume
• Symptoms suggestive of diabetes plus – Correction of acid-base status
j Random plasma glucose ≥ 200 mg/dL (or) – Correction of Dyselectrolemia
j Fasting plasma glucose ≥ 126 mg/dL (or) – Treatment of hyperglycemia
292
mebooksfree.com
j Initial lab evaluation should include should be avoided. Target of therapy is to slowly
– Blood sugar, blood and/or urine ketone reduce blood sugar by 50-100 mg/dL every hour
– Serum Electrolytes - Sodium, potassium, j The endpoint for stopping insulin infusion is
chloride, bicarbonate, calcium and phosphorus correction of acidosis and not just hyperglycemia.
– Electrocardiogram, ABG analysis 5% dextrose is added to rehydration fluid when
– Blood culture and urine microscopic blood glucose dips below 250–300 mg/dL
examination. j After correcting acidosis, subcutaneous insulin
Classification of severity in DKA is started at a dose of (0.2–0.4 units/kg). Insulin
infusion is stopped after 30 minutes and oral
Blood glucose Arterial Serum HCO3 feeding is resumed.
mg/dL pH mEq/L j This regimen of insulin plus meal is carried out
every 6–8 hours until the child can feed orally.
Mild DKA 200 - 250 7.24 – 7.3 15 – 18
j Two daily doses (before breakfast and dinner)
Moderate >250 7.0 – 7.2 10 – 15 of regular plus intermediate acting NPH insulin
DKA are started. Additional lunch time dose of plain
Severe >250 <7.0 <10 insulin may be required.
DKA • Monitoring during DKA
j Vitals, hydration, sensorium, urine output should be
Treatment of mild DKA (200-250 mg/dl glucose, mild continuously monitored during rehydration phase
dehydration, pH 7.2-7.3 and bicarbonate 10-15 mmol/L) j Serial monitoring of Serum glucose, sodium,
• Oral rehydration with sugar free fluid potassium, bicarbonate, phosphorus and urine
• Insulin therapy: 1 - 2 units/kg of soluble insulin ketones are required
(50% dose given intravenously and other 50% Complications
subcutaneously followed by 20% of the initial dose • Acute gastric dilatation
every 1 to 2 hours subcutaneously. • Thrombo-embolism
Treatment of Moderate and Severe DKA • Cerebral Edema
• Fluid Resuscitation and Correction of j Usually occurs during insulin therapy
Dyselectrolemia j Etiology
j Hypotension is treated with boluses of – Rapid correction of hyper-osmolality
10-20 ml/kg of 0.9 normal saline – Sodium bicarbonate infusion
j For moderate to severe dehydration, replacement – Elevated blood urea
of 75-85 ml/kg fluid for 48 hours is indicated. – Severe hypocapnia
Normal Saline is the crystalloid fluid of choice for – Lack of rise of serum sodium during treatment.
initial volume expansion. Half normal saline is j Clinical features
started after 6 hours of rehydration. – Early features include altered mentation,
j Potassium (40 mEq/L) should be added to the headache, vomiting, bradycardia and
rehydration fluid after ruling out hyperkalemia. hypertension
– Late features include pupillary changes,
• Sodium bicarbonate therapy
papilledema and UMN findings
j Routine sodium bicarbonate infusion is
j Treatment
contraindicated due to severe adverse effects like
– Confirmation with CT brain
– Cerebral edema
– Prompt therapy with IV Mannitol
– Hypokalemia
C) Post acidosis therapy
– Left shifting of oxygen dissociation curve
j Management of precipitating factor – Infection or
– Metabolic Alkalosis
emotional stress
j Sodium bicarbonate is only indicated in cases of
– Send cultures, septic screen
refractory severe metabolic acidosis (pH< 6.9) not
– Start empirical Antibiotics
responding to rehydration
j Subcutaneous insulin therapy – as discussed above
j Dose of Sodium bicarbonate in ml = 0.15 × base
j Nutrition
deficit × kg body weight. It is given as infusion over
– Approximately – 1000 calories at 1 year if age,
2 hour period and stopped when pH reaches 7.0
additional 100 cal/year till puberty
• Insulin Therapy j Education of family for home management of
j Current preferred treatment of choice is DM and Monitoring
Continuous low dose insulin infusion. – Blood glucose monitoring at home (Fasting,
j Regular insulin is given along with normal saline prelunch, predinner, bedtime)
at the rate of 0.1units/Kg/hour. Insulin boluses – HbA1C once in 3 months
293
mebooksfree.com
Psychological and social support for the patient

Table 17.4 Common causes of hypothyroidism
j
and the family

– Multidisciplinary Team involving doctors,
Primary hypothyroidism Secondary
diabetes nurse/educators, dietician,
psychologist and social worker. • Autoimmune – Hashimoto Hypothalamo
– Increasing awareness and educating about thyroiditis, Autoimmune pituitary disease
Diabetes, nutrition, monitoring, and polyglandular syndrome (APS) • Panhypopituitarism
hypoglycemia, • Thyroid dysgenesis (aplasia, • Trauma
– Exercise as well as management during days of hypoplasia, ectopic thyroid) • Post-surgical
unrelated sickness • Thyroid Dyshormonogenesis • Neoplastic
• Iodine deficiency • Infection
Complications
• Drug induced- Amiodarone, • Radiation
A) Hypoglycemia –
phenytoin, methimazole,
j Blood glucose <60 mg/dl
propylthiouracil
j Clinical features:
• Irradiation
– Neuroglycopenic symptoms like drowsiness, • Thyroid surgery
confusion, stupor, coma or seizures
– Pallor, sweating, tremors and tachycardia
j Treatment 17.4.1 Congenital hypothyroidism
– Immediate ingestion of simple sugar (5-10 g) (CH)
in the form of glucose, fruit juice or carbonated
milk. • Most commonest type of hypothyroidism seen in
– Symptomatic or drowsy child should be treated children. Clinical features are present since birth or
with 0.5 mg of s.c glucagon early infancy.
B) Somogyi Phenomenon and Dawn Phenomenon • Incidence of CH in India is approximately 1 in 3000
j Somogyi phenomenon: Insulin induced live births
nocturnal hypoglycemia leading on to early • CH is the most common preventable cause of mental
morning rebound hyperglycemia. This occurs due retardation in children
to excess counter-regulatory hormones in response Etiology
to hypoglycemia. • Thyroid dysgenesis is the most common etiology
j Dawn Phenomenon: Moderate hyperglycemia accounting for 85% cases. The term dysgenesis includes
seen early in the morning. It is due to nocturnal complete aplasia, hypoplasia or an ectopic thyroid
growth hormone mediated clearance of insulin. gland. Exact cause of dysgenesis is not known. Genetic
In physiological state, this phenomenon is and Immunological factors may play a role in genesis.
easily compensated with increased insulin • Approximately 98% of cases occur sporadically while
output. 2% are familial.
Screening for Long Term Complications • Other causes include
j Dyshormonogenesis - Inborn errors of thyroid
Microvascular Macrovascular hormone synthesis
j Deficiency of Iodine
• Retinopathy • Cerebrovascular j Congenital anomalies of thyroid gland
• Nephropathy disease j Disorders of thyroid metabolism
• Neuropathy • Peripheral vascular j Pituitary and hypothalamic dysfunction
disease
• Associated syndromes
j Pendred Syndrome: Autosomal recessive disorder
characterized by sensorineural deafness and goiter.
j Kocher Debre Semelaigne syndrome:
Hypothyroidism associated with muscular
17.4 Hypothyroidism pseudohypertrophy especially in calf muscles
Clinical features
• Hypothyroidism in children may be congenital or • Early manifestations include hypotonia, hoarse cry,
acquired decreased activity, wide anterior fontanelle, prolonged
• Hypothyroidism is also classified as primary (thyroid hyperbilirubinemia and decreased passage of stools
disease) or secondary (Pituitary or Hypothalamic or constipation.
dysfunction)
• Examination reveals coarse facial features (Figure 17.2),
• Common etiology of hypothyroidism are large protruding tongue, umbilical hernias and mottled,
summarized in Table 17.4 cold and dry skin (Cutis marmoratus).
294
mebooksfree.com
• Imaging: Ultrasound examination to confirm normal

location of thyroid gland and to rule out ectopic
thyroid in lingual or sublingual areas.
Differential diagnosis
• Down syndrome
• Pituitary dwarfism
• Mucopolysaccharidosis
Treatment
• Management is aimed at early diagnosis and
immediate exogenous replacement of thyroid
hormone
• All cases of confirmed hypothyroidism should
promptly receive thyroid hormone supplementation
regardless of the etiology.
• Drug of choice is synthetic oral levothyroxine
(Eltroxin). It is started at a dose of 10-15 mcg/kg/day
• Adequacy of therapy is indicated by increased activity,
relief from constipation, improving appetite and
feeding.
Follow up and prognosis
• Thyroid profile should be done at 4 weeks after
starting therapy and every 3 months following that.
• For cases where thyroxine was started for minimally
abnormal values, once euthyroid state is achieved
within few months of therapy, thyroxine can be
tapered and stopped. These cases should be closely
followed for any features of hypothyroidism (Thyroid
Figure 17.2 Coase facial features in congenital hormone assay and clinical symptoms)
hypothyroidism. • Early diagnosis and starting treatment in first few
(Picture Courtesy: Dr. J. Dhivyalakshmi, SRMC Porur, Chennai). weeks of life results in best outcomes. Linear growth
and intelligence are invariably normal in this group.
Infants with delayed detection often have varying
• Most affected infants are asymptomatic at birth. degrees of growth failure, cognitive deficits and
Symptoms evolve during the first few months and full mental retardation.
blown clinical features are visible by 3 – 6 months.
• These children also have delayed dentition, poor
feeding, short stature and poor growth 17.4.2 Acquired hypothyroidism
• Untreated children have severe involvement • Hypothyroidism acquired beyond infancy is
with myxedema, severe mental retardation, most commonly due to autoimmune thyroid
developmental delay, growth failure and goiter disease known as Hashimoto thyroiditis (Chronic
termed as cretinism. lymphocytic thyroiditis)
Diagnosis • Children present beyond 5 years of age
• Neonatal Screening: Clinical manifestation
j Demonstrating decreased total or free T4 and • Short stature due to deceleration of growth may be
elevated TSH levels. Total TSH levels >20 mU/L is the earliest presenting feature. Other classical features
diagnostic. include cold intolerance, constipation, lethargy and
j Assay should be done after 72 hours of life excessive sleepiness.
(3 -5 days) in order to prevent false positive • Myxedematous change of the skin, unexplained
diagnosis due to postnatal physiological rise in anemia, precocious or delayed puberty
TSH levels seen in first 48 hours. • Pseudotumour cerebri, muscle weakness, muscular
j Thyroid-binding globulin (TBG) deficiency hypertrophy, nerve entrapment and ataxia
manifests with reduced total T4 levels and normal • Delayed dental and skeletal maturation.
TSH levels • Some children present with goiter which is typically
• Epiphyseal dysgenesis: Absent distal femoral and non tender and firm, with a rubbery consistency and
proximal tibial epiphysis in term babies. a pebble surface
295
mebooksfree.com
Investigations: Treatment:
• Thyroid hormone assay: Serum Free T4, T3 Medical:
and TSH – Compare with age specific reference • Anti-thyroid drugs (propylthiouracil or carbimazole)
ranges or radioactive iodine
• Assay of Anti-thyroglobulin and anti-peroxidase • Saturated solution of Potassium iodide (1 drop per
antibodies – Autoimmune thyroiditis day) may be added
• Imaging: Ultrasound examination of thyroid • Symptomatic control with B blockers (propranolol),
• Radioactive iodine uptake scan • In the thyro-toxic state severe, parenteral fluid therapy,
• Bone age assessment corticosteroids and digitalization may be indicated if
• Hyponatremia, Macrocytic anemia heart failure occurs.
• Hypercholesterolemia and elevated CPK Surgery
Complications • Subtotal thyroidectomy
• Heart failure • Complications of surgery - Hypoparathyroidism,
• Hyponatremia vocal cord paralysis
• Adrenal insufficiency Prognosis
• Coagulopathy (acquired Von willebrand disease) • Advanced osseous maturation, microcephaly and
Treatment cognitive impairment may occur in cases of delayed
• Principles are similar to treatment of congenital treatment
hypothyroidism • In some cases, fetal hyperthyroidism may suppress
• Hormonal replacement with synthetic oral hypothalamic pituitary thyroid feedback mechanism
levothyroxine is the treatment of choice leading to permanent central hypothyroidism,
• Dose of Levothyroxine requiring lifelong hormone replacement
j 1 – 3 yr of age = 4 - 6 ug/kg/day
j 3 – 10 yr of age = 3 - 5 ug/kg/day
10 - 16yr of age = 2 - 4 ug/kg/day
17.6 Hyperthyroidism
j
• Drug overdosage leads to diarrhea, restlessness,

insomnia, abdominal pain, vomiting, polyuria and
tremors. • It results from excessive secretion of thyroid
hormone during childhood
• Most common cause in children is Grave’s disease
which is often due to diffuse toxic goitre
17.5 Neonatal Grave’s disease • Etiology
j Grave’s disease
Etiology j McCune-Albright syndrome
• Congenital hyperthyroidism is caused by j Infants born to mothers with Grave’s disease
transplacental passage of TRSAb antibodies j Sporadic thyroiditis
• Very high levels of TRSAb j Thyrotoxicosis factitia
• Maternal Grave’s disease is associated in most cases j TSH secreting adenomas and
Hyper functioning thyroid carcinoma
Clinical features
j
• These babies are classically premature, IUGR, goiters,

exophthalmos, microcephaly. They are irritable,
17.6.1 Graves’ Disease
hyperalert and may have tachycardia, tachpynoea,
hyperthermia, jaundice, hepatosplenomegaly • Autoimmune disease resulting in excessive secretion
increases and severe hypertension progress to cardiac of thyroid hormones due to thyroid stimulating
decompensation antibodies.
• Advanced bone age, frontal bossing with triangular • Most cases occur during 11-15 years and girls are
facies and cranial synostosis are common. commonly affected
• Propranolol is used to treat maternal thyrotoxicosis, Etiology
can cross placenta resulting in respiratory depression • The exact mechanism for autoimmunity is not known.
in neonates • Stress, environmental factors, infection and exposure
Investigations: to certain chemicals may play a role
• Free T4 and T3 elevated • Two antibodies are commonly found in this condition
• TSH decreased j TRSAb (Thyroid receptor stimulating
• TRS Ab found in Grave’s disease antibody) - stimulates TSH receptor leading
296
mebooksfree.com
on to thyroid hyperplasia and excessive production Propylthiouracil

j
of thyroid hormones Propanalol (0.5-2.0 mg/Kg/24 hr orally, divided

j
j TRBAb (thyroid receptor blocking antibody). three times daily) in severe involvement
• The opthalmoligical findings are due to antibodies • Indications for Radioiodine treatment
reacting with TSH receptors found in retroorbital or Surgery
adipocytes. These antibodies bind to extra-ocular j Poor compliance with medical therapy
muscles and orbital fibroblasts stimulating the j When medical therapy fails to achieve remission
synthesis of glycosaminoglycans. j When side effects of medical therapy are very
• Associated with other auto-immune diseases like severe
Addison disease, type I DM, vitiligo and alopecia • High dose Prednisolone for treatment of
areata Ophthalmopathy
Clinical Manifestations
• Earliest manifestations include emotional
disturbances and motor hyperactivity. 17.7 Hypoparathyroidism
• Insiduous onset of diffuse, smooth and soft thyroid
goiter is pathognomonic.
• Hand tremors, restlessness, insomnia, increased • Occurs due to absent or low levels or reduced
appetite and reduced attention span peripheral action of parathormone (PTH)
• Characteristic ocular findings include lagging of Etiology
the upper eyelid in downward gaze, impairment of • Transient deficiency of PTH in newborn
convergence, retraction of the upper eyelid, infrequent • Reduced secretion of PTH
blinking, chemosis and decreased visual acuity j Aplasia or hypoplasia of parathyroid gland
• Flushed skin with excessive sweating j Autoimmune hypoparathyroidism
• Cardiovascular manifestations include tachycardia, • Suppression of PTH secretion from parathyroid
palpitations, dyspnea and cardiac enlargement. j Maternal hyperparathyroidism
Other findings are atrial fibrillation, papillary muscle j Severe magnesium deficiency
dysfunction and hypertension. Severe involvement • PTH gene mutation
can lead to high output cardiac failure. • Pseudo hypoparathyroidism (Defective end organ
• Brisk deep tendon reflexes (hyperreflexia), especially response to PTH)
during the return phase • Secondary causes:
Thyroid Crisis or Storm j Post-surgical removal
• Acute onset, hyperthermia, tachycardia, heart failure j Accumulation of iron or copper in parathyroid
and restlessness glands—Thalassemia and Wilson’s disease
• Rapid progression to delirium, coma and death • Associated diseases—Kearns Sayre syndrome, HDR
• Aggravated by trauma, infection, radioactive iodine syndrome
treatment or surgery Clinical Features
Laboratory Findings • Musculoskeletal pain, cramps followed by numbness,
• Thyroid hormone assay: Elevated serum levels of T4, stiffness and tingling sensation hands and feet are the
T3, free T4 and free T3. TSH levels are reduced. presenting symptoms in most cases
• Assay of anti-thyroid antibodies – • Chvostek sign (twitching of the mouth,
j Anti- thyroid antibodies including thyroid alaenasi and orbicularis oculi when facial nerve
peroxidase are often present is tapped) or
j Measurement of thyroid stimulating immunoglobulin • Trousseau sign (carpal spasm is elicited when blood
or thyrotropin binding inhibitory immunoglobulin pressure cuff tied on the arm and inflated it between
• Bone age assessment - Advanced bone maturation systolic and diastolic pressure for 3 min) or laryngeal
• Reduced bone density and carpopedal spasms
• Radio-iodine uptake study with 123 iodine - Rapid, • Obstetric hand position—Hands and forearms
diffuse concentration in thyroid are affected assuming typical position—adduction
Treatment of thumbs, flexion of metacarpophalangeal
and interphalangeal joints with flexion of wrist
• Main modalities of treatment include Antithyroid
drugs, surgery and radioiodine therapy. and elbow
• Antithyroid drugs • Raised ICT, papilledema, extrapyramidal symptoms,
j Methimazole: (0.25-1.0 mg/Kg/24 hr given once delayed dentition
or twice daily) • Increased risk of mucocutaneuos candidiasis
297
mebooksfree.com
Diagnosis • Cushing syndrome secondary to ACTH secreting

• Hypocalcemia (Serum calcium 5–7 mg/dL), pituitary tumor is known as Cushing disease
Hyperphosphatemia (7–12 mg/dL) • McCune-Albright syndrome is due to constitutional
• Alkaline phosphatase and Serum magnesium are activation of ACTH receptor secondary to somatic
usually normal or low. mutation of Gsα protein. Other features include
• Serum levels of Parathormone and 1,25 (OH2)D3 are low fibrous dysplasia, café-au-lait spots, hyperthyroidism
• Xray of bones occasionally show increased density of and precocious puberty.
metaphysis suggestive of heavy metal poisoning Clinical features
• CT Brain may reveal calcification of basal Ganglia
• Early features of CS include Growth failure and
• ECG: QT interval prolongation obesity.
• EEG: Widespread slow activity
• Phenotypic features
Treatment j Classical features such as central obesity, striae,
• Emergency treatment of tetany: 10% calcium gluconate, moon facies and buffalo hump. (Figure 17.3A, B).
IV infusion at the rate of 0.5–1.0 mL/min every 6–8 Centripetal fat distribution (Re-distribution of fat
h under cardiac monitoring followed by maintenance in face, neck and abdomen)
dose of 0.5–1 gm of oral calcium. j Thinning of skin with violaceous striae (seen in
• Oral Calcitriol and Calcium supplementation—800 the abdomen, buttocks, thighs, axilla) and easy
mg of elemental calcium should be given daily bruising
• Phosphorous rich food items like milk, eggs, and • Wasting of muscles and weakness
cheese should be reduced in diet • Hypertension, delayed puberty, lethargy, bone pain,
Differential Diagnosis osteoporosis and obsessive – compulsive behavioral
• Hypomagnesemia disorders
• Poisoning with inorganic phosphate, large doses of • Children with ectopic ACTH production:
laxatives or sodium phosphate enemas j Hyperpigmentation, Hypokalemic alkalosis
• Tumor lysis syndrome (when treating for Acute j Hypertension, Heart failure
lymphoblastic leukemia) • Children with Adrenal tumors:
j Abnormal masculinization, deepening
17.8 Cushing syndrome of voice
j Hirsutism on the face and trunk
j Pubic hair, acne, enlargement of clitoris
• The term Cushing syndrome is used to denote Diagnosis
a group of medical disorders characterized by • Cortisol levels are normally highest at 8 am and
adrenocortical hyperfunction. Clinical symptoms are decreases to less than 50% by midnight. This normal
due to prolonged glucocorticoid excess. circadian rhythm is lost. Suppressed basal cortisol
Etiology is classically seen with exogenous glucocorticoid
• Cushing syndrome is either due to exogenous supplementation. Midnight cortisol > 4.4 μg/dL
administration (Most common cause) or suggests diagnosis.
endogenous hypersecretion of glucocorticoids. • Elevated night-time salivary cortisol levels
Endogenous hypersecretion can be either due to • Urine 24 hr free cortisol is increased (expressed as
primary over functioning adrenal gland or secondary ratio of µg of cortisol excreted per gram of
to pituitary/hypothalamic disease with increased creatinine)
ACTH secretion • Serum Sodium, potassium and alkalosis
ACTH dependent ACTH independent Exogenous

• Hypothalamic: • Adrenal tumors: Carcinoma, Glucocorticoid supplementation
j Tumour secreting CRH adenoma (Most common cause): High dose or
• Pituitary: • Macronodular adrenal prolonged oral, parenteral, topical
j Increased ACTH production hyperplasia or inhalational
j Micro or Macroadenoma • Primary pigmented nodular
(Cushing’s disease) adrenal hyperplasia (Carney
• Ectopic: Complex)
j Neuroblastoma, Islet cell • McCune Albright syndrome
tumor
j Carcinoids, Wilms tumor
298
mebooksfree.com
• Low dose and high dose Dexamethasone

suppression test:
j IV bolus of CRH
– Exaggerated ACTh and cortisol response in
Cushing syndrome
– No increase in ACTh and Cortisol in Adrenal
tumors
j Second step dexamethasone suppression test
– Administration of 30 and 120 ug/kg/day in 4
divided doses on consecutive days
– Suppress serum levels of cortisol – Cushing
syndrome/pituitary
– No suppression - ACTH independent Cushing
syndrome
j Imaging - Adrenal CT scan / USG of Adrenal glands
j Pituitary MRI Scan with Gadolinium contrast
j Bilateral inferior petrosal blood sampling
j Impaired glucose tolerance test
Treatment
• Adrenal gland tumour resection
j Unilateral adrenalectomy for unilateral adenoma
j Subtotal adrenalectomy for bilateral adenoma and
carcinoma
j Recovery of residual adrenal gland may take upto
6 months
• Trans-sphenoidal pituitary resection is the treatment
of choice for pituitary adenomas
• Relapses are treated with re-operation or pituitary
irradiation
• Medical therapy commonly used in adults like
Cyproheptadine, serotonin antagonist that blocks
ACTH release are rarely used in children
• Nelson Syndrome
j Occurrence of pituitary macroadenomas many
years after bilateral adrenalectomy, causing high
ACTH levels and skin hyperpigmentation
17.9 Adrenal insufficiency

Figure 17.3 (A) Facial features of Cushing syndrome.
(B) Striae of Cushing syndrome.
(Picture Courtesy: Dr. J. Dhivyalakshmi, SRMC Porur, Chennai). • This condition is caused by deficiency of adrenal
cortical hormones especially cortisol.
• This is relatively rare in children but potentially life-
• Overnight dexamethasone suppression test: threatening
j Single dose 25–30 µg/kg given at 11PM
j Plasma cortisol level< 5 µg/dl at 8 AM is Normal Classification
j Elevated in Cushing’s disease • Primary - Abnormality of adrenal gland—Primary
• Midnight serum ACTH levels adrenal insufficiency or Addison disease
• Secondary - Due to defects in the hypothalamus or
20-80 ng/L pituitary gland—Secondary adrenal insufficiency.
<10 ng/L >100 ng/L
Etiology
ACTH Normal/high in High in ectopic
independent ACTH ACTH
• Acute:
j Sudden steroid withdrawal
(cortisol dependent production
Sepsis
secreting (pituitary
j
tumor) adenomas) j Severe hypotension

j Trauma
299
mebooksfree.com
• Chronic: Treatment
j Primary (ACTH increased) • Acute Adrenal crisis
– Congenital Adrenal hyperplasia j Immediate IV fluids to treat hypotension and salt
– Metabolic: Adrenoleukodystrophy, Zellweger replacement
syndrome, Wolman disease j Glucose infusion to treat hypoglycemia
– Destruction of adrenal cortex (Addison disease) j Antibiotics if necessary
due to Autoimmune disease j Glucocorticoid: Hydrocortisone IV – 50–75 mg/m2
– Infiltration: Leukemia, Histiocytosis, initially, followed by 8–10 mg/m2/day in four doses
Sarcoidosis, Amyloidosis or as a continuous infusion.
– Infections: HIV, Tuberculosis, Histoplasmosis, • Long term therapy
Waterhouse–Friderichsen syndrome j Daily hydrocortisone and fludrocortisone
(B/L Adrenal hemorrhage and failure in j Glucocorticoid: Maintenance doses with oral
meningococcemia) prednisolone
– Drugs, eg. Ketoconazole j Mineralocorticoid: Fludrocortisone –
j Secondary (ACTH decreased) 0.05–0.15 mg/day.
– Pituitary or hypothalamic disease • Cessation of Glucocorticoid therapy
– Long term steroid therapy j Long term steroids suppress CRH and ACTH
Clinical Features secretions leading to decreased ACTH and adreno-
cortical atrophy.
• Affected children present with non-specific signs and
symptoms leading on to delayed diagnosis j ACTH stimulation test to confirm recovery
of adrenal glands prior to stopping exogenous
• Acute insufficiency (Addison’s disease) presents
with altered mental status, dehydration, tachycardia, steroids
hypotension, peripheral circulatory failure and
cyanosis. Acute adrenal crisis is often precipitated
by infection, trauma and abrupt steroid cessation in
children receiving long-term replacement therapy.
17.10 Congenital adrenal
• Infants with chronic insufficiency present with hyperplasia
irritability, apathy, drowsiness, vomiting, defective
growth, hypoglycemia and dehydration leading to Etiology
eventual circulatory collapse and coma. • CAH includes a group of disorders with deranged
• Older children present with weakness, fatigue, adrenal corticosteroid biosynthesis due to
anorexia, nausea, vomiting, abdominal pain, deficiency of one or several enzymes involved
diarrhea, reduced growth velocity, postural (Figure 17.4).
hypotension and salt craving • Autosomal recessive inheritance
• Hyperpigmentation of buccal mucosa, skin creases • Occurs due to deficiency of enzymes in the
and scars occur with primary disease secondary to cholesterol to cortisol biosynthesis pathway-
ACTH increased levels (Addison’s disease) j 21-hydroxylase – Most common
• Secondary cases present with features of pituitary and j 11 beta hydroxylase
hypothalamic disease j Others - 3 beta hydroxysteroid dehydrogenase,
Investigations 17 alpha hydroxylase and cholesterol
• Serum electrolytes - Hyponatremia and hyperkalemia desmolase
(due to aldosterone deficiency) • Enzymes involved in the adrenal androgen
• Hypoglycemia (and gonadal) biosynthetic pathway include
• Primary disease (Addison’s disease) - Diagnostic criteria- j 17,20 desmolase
j Reduced cortisol levels < 10 µg/dL j 17 beta hydroxysteroid dehydrogenase
j Elevated ACTH levels >100 pg/mL j 5 alpha reductase
j Synacthen ACTH stimulation test Pathogenesis
• Secondary disease – • In CAH, reduced plasma cortisol leads to secondary
j Reduced cortisol levels < 10 µg/dL elevation of ACTH levels via the negative feedback
j Low ACTH levels mechanism.
j Insulin-induced hypoglycemia or CRH test • Clinical features are due to accumulation of hormone
j Pituitary hormone deficiencies precursors proximal to blocked metabolic pathway
• Adrenal imaging – Ultrasound /CT abdomen and deficiency of the hormones distal to the blocked
• MRI Brain – Secondary causes / Adrenoleukodystrophy pathway.
300
mebooksfree.com
Figure 17.4 Adrenal corticosteroid biosynthesis pathway.

Source: Adapted from Rang and Dale’s Pharmacology, 2012.
j Variable labio scrotal fold associated with

17.11 21-Hydroxylase deficiency urogenital sinus
j Hyperpigmentation of genital, nipple, umbilicus
• Most common form of CAH (>95%) and cliteromegaly
• Absence of 21 hydroxylase leads to accumulation of • Affected males are normal at birth but present later
17-hydroxyprogesterone on with penile enlargement, rapid growth during first
• Symptoms are due to cortisol deficiency and decade (Relative tall stature) and advanced skeletal
secondary elevated of ACTH leading on to maturation (premature fusion of epiphysis leading on
adrenocortical hyperplasia to short stature)
• Blocked mineralocorticoids and glucocorticoids leads • There is no hypertension
to shunting of precursors into androgen pathway • Classical salt wasting – Accounts for 75% cases.
• Two genes encoding CYP21B (active) and CYP21A Presents early in infancy with severe renal wasting
(inactive) to the short arm of chromosome 6 of sodium, vomiting, dehydration, hypovolvemia
and ambiguous genitalia (Figure 17.5). Symptoms
Clinical Features
are due to excessive adrenal androgens (virilization
• Most common presentation is masculinization of of female external genitalia), cortisol deficiency,
genotypic female. Most cases are recognized at birth
aldosterone deficiency (salt wasting and
due to ambiguous external genitalia
hypovolvemia) and accumulation of precursors like
• Severe cases resemble phenotypic males but have 17-hydroxyprogesterone (natriuresis). About 25%
j Female internal gonads – Ovaries, fallopian tubes
cases present with simple virilizing type without salt
and uterus
wasting.
301
mebooksfree.com
j Glucocorticoid supplementation suppresses excess

production of androgens by the adrenal cortex
and minimizes problems such as excessive growth,
skeletal maturation and virilization.
j Monitoring for drug toxicity, pubertal
development, evaluating skeletal maturation by
serial radiographs of hands and wrist for bone age
is necessary for optimal treatment
j Non-classical cases may not require treatment or at
very low doses
• Mineralocorticoid replacement
j For those with salt wasting type
j Fludrocortisone 0.1-0.3 mg (100–300 µg) daily in
2 divided doses
j Sodium chloride supplementation (8 mmol/kg)
j Monitoring of vital signs (tachycardia &
hypertension – overtreatment), serum
Figure 17.5 Ambiguous genitalia. electrolytes and plasma renin to ensure adequacy
of therapy
• Other measures
j Antiandrogen – Flutamide
• Non-classical (Late onset) – Symptoms are j Aromatase inhibitor – anastrazole
variable, mild and often present late before puberty. j Growth hormone with or without LHRH agonist
Suspected girls present with hirsutism and infertility.
• Surgery for ambiguous genitalia – Feminizing
Cases present with premature pubarche, rapid genitoplasty in females.
growth (and reduced height prognosis), male type
• Prenatal treatment – Dexamethasone 20 ug/kg of
baldness in female, delayed menarche or secondary pre-pregnancy weight to prevent external genital
amenorrhea virilization in female fetus
Laboratory Diagnosis • Appropriate Sex Assignment
• Newborn screening for elevated levels of 17 hydroxy j With appropriate therapy, female can fertile
progesterone (17-OHP) 11-beta hydroxylase deficiency
• Reduced serum cortisol • Account for 5% cases (second commonest type after
• Plasma ACTH, androstenedione, testosterone and 21 hydroxylase deficiency)
urinary pregnanetriol levels are raised • 11-Deoxycorticosterone (11-DOC) and
• Salt wasting form – 11-deoxycortisol levels are raised. These metabolites
j Hyponatremia, Hyperkalemia, increased urinary have mineralocorticoid activity.
sodium loss • Cortisol and corticosterone are deficient
j Low serum aldosterone levels, high renin levels • 11-DOC leads to sodium and water retention,
j Hypoglycemia, acidosis and uremia hypervolvemia and Hypertension
Management • Hypokalemic alkalosis
• Basic principles of management are to suppress • Lab diagnosis: Elevated 11-DOC levels and urinary
overproduction of precursor hormones and to replace metabolites
deficient steroids • Treatment with Glucocorticoids
• Glucocorticoid replacement
j Hydrocortisone – 10-20 mg/m2/24 hr daily oral in Online supplementary materials:
3 divided doses Please visit MedEnact to access chapter wise MCQs and
j During periods of stress (infection or surgery), previous year pediatrics theory questions asked in various
doses have to be doubled final MBBS University examinations.
302
mebooksfree.com
Chapter | 18 |
Pediatric oncology
Immunologic classification
18.1 Acute lymphoblastic • Done by flow cytometry to define cell lineage
leukemia (ALL) • Used to subclassify ALL into pre-B-ALL, mature
B-cell ALL and T-cell ALL.
Epidemiology
• Myeloid- associated antigens (CD13 and CD33) are
expressed.
• Malignant disorder originating in a single B or T
lymphocyte progenitor
• Helps to monitor minimal residual disease (MRD)
• ALL is a heterogeneous group of malignancies with Genetic classification (cytogenetic and molecular):
distinctive genetic abnormalities • Based on gene rearrangement and translocation
• Incidence: 3–4 cases per 100,000 per year • Identifies the risk group stratification of childhood
• Peak incidence at 2–3 year of age, predominant in ALL
Caucasians and males. • Helps to guide therapy
• Incidence risk is higher in children with • Risk group includes
chromosomal abnormalities and monozygotic twins. j t (12.21)
j Down’s syndrome, Bloom syndrome j BCR-ABL
j Fanconi anemia, Ataxia – telangiectasia j Hypodiploidy
j MLL translocation
Classification
j Trisomies of chromosome 4,10 and 17
• Classified based on
j Morphological and cytochemical classification
• Hyperdiploidy has favourable outcome than
hypodiploidy
j Immunologic classification
j Genetic classification (cytogenetic and Etiopathogenesis
molecular) • Caused by
j Postconception somatic mutations in lymphoid
Cytogenetics
cells
• Morphological and cytochemical classification j Leukemia-specific fusion-gene sequences in
j First step in diagnosis of ALL
neonatal blood spots.
j L3 morphology expresses surface immunoglobins
j Exposure to diagnostic radiation both in utero
– 85% as B lymphoblastic leukemia, 15% as
and in children
T- lymphoblastic leukemia, 1% derived from
j An association between B-cell ALL and Epstein-
matured B cells or Burkitt leukemia
Barr viral infections.
303
mebooksfree.com
Initiation and progression of ALL is driven by:
Clinical Features • Bone: Extreme tenderness, joint swelling, effusion.

• Anorexia, fatigue, malaise, irritability and fever due to • Lymphadenopathy, Hepatosplenomegaly
release of pyrogenic cytokines. • Testicular enlargement, Listlessness
• Bone pain: • Papilledema, Focal neurological signs
j Typically involving long bones Lab diagnosis
j Results from direct infiltration of periosteum, • Blood film: Profound neutropenia,
bone infarction or expansion of marrow cavity by hyperleukocytosis, thrombocytopenia and circulating
leukemic cells. lymphoblasts
• Painless enlargement of scrotum in infants with ALL • Signs of tumor lysis:
and T-cell ALL hyperleukocytosis. j Elevated uric acid, hyperkalemia,
• Organ infiltration causing lymphadenopathy, hyperphosphatemia, hypocalcemia
hepatosplenomegaly and priapism j Elevated lactogen dehydrogenase (LDH)
• CNS involvement: j Elevated liver enzymes
j Increased intracranial pressure j Increased serum creatinine reflecting deposition
j Cranial nerve palsies (CN VI palsy) of uric acid/calcium in renal tubules or leukemic
j Chloromas of spinal cord infiltration.
j Hypothalamic syndrome • Imaging
• Superior vena cava (SVC) syndrome, due to a j USG – to diagnose testicular enlargement
enlarging mediastinal mass j Chest radiograph- assess mediastinal mass in
• Respiratory distress due to mediastinal node T-ALL
compressing the airways. j Skeletal radiography- shows metaphyseal banding,
• Leukostasis (large number of deformable blasts periosteal reactions, osteolysis, osteosclerosis and
plugging the microcirculation). osteopenia
Physical exam j CT chest: in suspected superior mediastinal syndrome
• Pallor, Mucous membrane haemorrhage j CT spine: in suspected vertebral collapse
• Skin: purpuric and petechial skin lesions • Diagnostic procedures
304
mebooksfree.com
Pediatric oncology Chapter | 18 |
j Bone marrow aspirate showing lymphoblasts • Risk stratification on day1 based on National
j Immunophenotyping Cancer Institute Criteria (NCI)
• CSF analysis: • Assess response after 29 days of induction therapy
j CNS 1: <5 WBC’s/mm with no blasts • High risk groups require stem cell transplantation
j CNS 2: <5WBC’s/mm with blasts Chemotherapy Schedule
CNS 3: >5WBC’s/mm with blasts.
j
• Induction:
• Differential diagnosis: j 4 weeks duration
j Glucocorticoids, vincristine, L-asparaginase,
Non malignant Malignant Anthracycline, intrathecal chemotherapy
Infections conditions Conditions • Consolidation:
• Infectious • Juvenile • Neuroblastoma j 4–8 weeks
mononu- rheumatoid • Rhabdomyo- j Focuses on CNS prophylaxis
cleosis arthritis sarcoma j Drugs: cyclophosphamide, 6-mercaptopurine
• Epstein-Barr • Aplastic • Retinoblas- (6-MP) or 6-thioguanine with cytarabine
virus anemia toma • Interim maintenance:
• Parvovirus • Hyper- j 8 weeks
• Parapertusis eosinophilic j More intensified maintenance therapy
syndrome • Delayed Intensification (re-intensification and
reconsolidation): 8 weeks
Management • Maintenance:
Principles j 2.5 years in girls and 3 years in boys.
• Intensive chemotherapy for 6 months followed by j Involves daily oral 6-MP/ weekly oral methotrexate
2–3 years of oral therapy and 3 monthly vincristine with steroids.
Supportive Care In Management of ALL
Complications Management
Infections • Broad spectrum antibiotics
• Antifungal therapy after assessment
• Maintaining oral and perianal hygiene
• Prophylaxis for pneumocystis carnii
Bleeding • PLT transfusion
• Correction of coagulation defects
Anemia (Hb < 8 g/dl) • PRBC transfusion
Hyperleukocytosis • Hydration
• Platelet transfusion
• Exchange transufusion
• Respiratory support with oxygen
Tumour lysis syndrome • Maintain good urine output and alkaline pH
• Allopurinol to decrease uric acid production
• Rasburicase to prevent renal shutdown
• Correction of electrolyte imbalance
Phase of therapy Drugs used Features

Remission Induction • Vincristine • Characterised by 2–3 wks of neutropenia
• L-asparaginase • 90%–95% children achieve remission.
• Daunorubicin
• Methotrexate
• Prednisolone/ dexamethasone
Consolidation • Methotrexate • Consolidates the remission by further
• Cyclophosphamide decreasing the cell burden
• Cytosine arabinoside
• 6-mercaptopurine
• 6-Thioguanine
305
mebooksfree.com
Phase of therapy Drugs used Features

Cranial Prophylaxsis • Intrathecal instillation of methotrexate, • Instillation of chemotherapy and use of
cytosine arabinoside & hydrocortisone irradiation in high risk prevents CNS
• Cranial irradiation relapse
Delayed • Methotrexate • Serves as a boost
Intensification • Cyclophosphamide
• Cytosine Arabinoside
• 6MP
• 6TG
• Prednisolone/dexamethasone
Maintenance • Oral Methotrexate • Eliminates residual
• 6MP leukemia cells
Prognosis • Peak incidence in children < 2 years of age

• Long term survival: • Equal sex preponderance
j Overall: approaches 90% • Ratio of AML: ALL is 1:5
j Low-risk patients: 90%–95% • Risk factors includes:
j Standard risk group: 85% j Ionising radiation
j High risk group: 60%–75% j Chemotherapeutic agents
j Very high-risk group: 20%–50% j Organic solvents
j Infant group: 50% j Paroxysmal nocturnal hemoglobinuria
j Chromosomal abnormalities
Classification
18.2 Acute myeloid leukemia (AML) • 2 types:
• French-American – British classification (FAB):
j Consists of morphologic, cytochemical and
Epidemiology immunophenotypic criteria
• AML is a clonal hematopoietic stem cell disease. j Defines 8 subtypes (M0–M7) of AML
• Characterised by proliferation of non-functional • WHO classification (2008):
myeloid precursors called blasts in the bone marrow. j Current recommendation
• Incidence: 15%–20% in children < 20 years of age. j Includes cytogenetics
FAB
subtype Morphology Flow cytometry Cytogenetics Comments
M0 • Poorly differentiated • Anti-MPO,CD13+, Complex • 1%–5% of
AML CD33+,CD34+ cytogenetics pediatricAML
• Hypercellular marrow • Absence of lymphoid and • Poor prognosis
> 90% blasts megakaryocytic markers
M1 • Hypercellular • Anti-MPO,CD13+, Monosomy • 10%–15% of
marraow CD33+,CD34+ 5,7 or pediatric AML
• Myeloblastic without trisomy 8 • Average
maturation prognosis
M2 • Myeloblast with Anti-MPO,CD13+,CD33+, t(8,21) • 20%–25% of
maturation CD34+,HLA-DR+ (22;q22) pediatric AML
• Represent > 30% of • Increased
bone marrow cells chloromas
• Presence of Auer rods
M3 • Abnormal Anti-MPO, CD13+,CD33+, t(15,17) • 3%–15%
promyelocytes CD11+,CD34-,HLR-DR- (q24;q21) pediatric AML
• Auer rods • Associated
• A hypogranular coagulopathy
variant • Favourable
• Strongly MPO and prognosis with
SBB+ ATRA
306
mebooksfree.com
FAB
subtype Morphology Flow cytometry Cytogenetics Comments
M4 • Myelomonocytic Myelomonocytic markers CD13,C Inv16 or • 15%–30% of
• Monocytic component D33,CD4,CD11b,CD14,CD15,CD t(16,16) pediatric AML
> 20% but < 80% of 64,HLA-DR (p13;q22) • Favourable
leukemic cells prognosis
• M4E0 associated
with > 5% abnormal
eosinophils
M5 • At least 80% of Monocytic markers such as Translocations 15%–20% of
leukemic cells are CD11b,CD14,CD15,CD64, involving MLL pediatric AML
monoblasts HLR-DR gene at 11q23 Hyperleukocytosis,
• Intense NSE locus DIC,extramedulary
activity,MPO-negative disease
M6 Erythroleukemia with • Glycophorin A+ Monosomy 5 • 1%–3%
erythroblast > 50% of or 7 or pediatric AML
total nucleated cells trisomy 8 • Poor prognosis
M7 • Megakaryocytic • Platelet peroxidase+ by electron T(1,22) • 4%–10% of
• Associated with microscopy (p13;q13) in pediatrric
marrow fibrosis • CD14+,CD61+ non-DS AML(mostly
• MPO-negative infants)
• Most common
in DS
• Unfavourable
prognosis
(except in DS)
WHO classification of AML

Environmental Inherited Acquired
Acute myeloid leukemia with recurrent chromosomal factors factors factors
translocations:
• AML with t(8;21)(q22;q22) AML-1 • Chemotherapy • Downs • A plastic anemia
• Acute promyelocytic leukemia: AML with t(15;17) • Pesticides syndrome • Myelodysplastic
(q22;q12) and variants • Petroleum • Fanconi syndrome
• AML with abnormal bone marrow eosinophils products anemia • Paroxysmal
• AML with 11q23 MLL abnormalities • Ionizing • Kostmann nocturnal
radiation syndrome hemoglobinuria
Acute myeloid leukemia with multilineage dysplasia:
• Diamond-
• With prior MDS
Blackfan
• Without prior MDS
syndrome
Acute myeloid leukemia with myelodysplastic
syndrome, therapy related:
• Alkylating agent related
• Epipodophyllotoxin related Pathophysiology
• Other types • Block in the differentiation of primitive myeloid
Acute myeloid leukemia,otherwise categorised: precursor
• AML minimally differentiated • Consists of 2 mechanisms:
• AML without maturation j Defect at the level of transcriptional activation
• AML with maturation j Defects in the signalling pathway of hematopoietic
• Acute myelomonocytic leukemia growth factors.
• Acute basophilic leukemia Clinical Presentation
• Acute panmyelosis with myelofibrosis Caused due to
• Replacement of bone marrow by malignant cells
Etiopathogenesis • Secondary bone marrow failure
• Exact cause is unknown in most cases • Children with AML presents with features of
• Predisposing factors for the development of AML are: j Marrow failure
307
mebooksfree.com
j Subcutaneous nodules or “blueberry muffin” j Electrolyte abnormalities: hyperkalemia/

lessions (infants) hypocalcemia/hyperphosphatemia/hyperuricemia
j Infiltration of the gingiva (monocytic subtypes) j CSF analysis for cell count and cytology
• Discrete masses – chloromas or granulocytic sarcomas Management
(AML with t8,21 translocation)
• LAB: disseminated intravascular coagulation
(Indicative of APL)
Symptoms Findings
• Fever 30-40% • Signs of anemia
• Pallor 25% • Thrombocytopenia
• Weight loss/ • Signs of infection
anorexia 22% • Hepatosplenomegaly
• Fatigue 19% • Lymphadenopathy
• Bleeding 33% • Gingival hyperplasia
• Bone or joint • Subcutaneous nodules
pain 18% • Chloroma – an
extramedullary collection
of leukemic cells that
presents as mass.
Diagnosis
Done by
• Bone marrow aspiration /Biopsy Induction Therapy
j Hypercellular marrow containing monotonous • Achieves morphological clinical remission
pattern of cells • 1-2 courses of induction are used
• Flow cytometry southern blotting: • Therapy consists of cytarabine (100 mg/m2/
j Identifies myeloperoxidase-containing cells day cont. infusion 7 days) + anthracycline
• Reverse transcriptase-polymerase chain reaction (daunorubicin 45–60 mg/m2 on day 1–3) in a 7 + 3
• Bone marrow aspirates: strategy
j >20% myeloblasts Post-remission therapy:
• LAB: • Low risk patients require 2–5 courses of chemotherapy
j Anemia, thrombocytopenia, leucocytosis with high dose cytarabine, anthracycline.
Peripheral smear with circulating myeloblasts,
j
• High risk patients, hematopoietic stem cell transplant
Auer rods (Figure 18.1) (HSCT).
Elevated prothrombin/partial thromboplastin in
j
• Intermediate-risk patients, either chemotherapy or
APL (M3) HSCT.
• Cytarabine and anthracycline (daunorubicin or
idarubicin) are gold standard for treatment of AML.
Phase of
therapy Drugs used Features
Remission Daunorubicin/ 3–4 weeks of
Induction Idarubicin neutropenia
Cytosine Risk of bacterial
Arabinoside and fungal infection
Etoposide Remission rate
70%–75%
Consolidation High dose Decreases the ma-
cytosine/ lignant cell burden
Arabinoside/
Mitoxantrone
Maintenance – Benefit of mainte-
nance therapy is
not proven
Figure 18.1 Auer rods.
308
mebooksfree.com
Prognosis: • Myeloid hyperplasia of bone marrow with

• 85% achieve remission with intensive extramedullary hematopoiesis
chemotherapy • Elevation of TLC
• 60%–70% achieve long term survival (>5 years after • Cytogenetic marker Philadelphia chromosome
diagnosis) (Ph1)
• Poor prognosis: • Formed by reciprocal translocation of chromosomes
j WBC > 100,000/microL 9 and 22
j Monosomy 7 • Giving rise to chimeris BCR-ABL fusion gene.
j Secondary AML Epidemiology
FLT3-ITD
j
• Constitutes 3% of newly diagnosed childhood
j Presence of multiple genetic translocation leukemia’s
mutations
• 1–2 cases per 75,000–100,000 population
Poor initial response to therapy (induction failure) or
j
• Male predominance
presence of >0.1% minimal residual disease (MRD)
• Reported between 0–14 years in males and
15–29 years in females
Pathogenesis: Consists of 3 phases
18.3 Chronic myeloid leukemia • Chronic phase
(CML) • Accelerated phase
• Blast phase
• Chronic hematopoietic stem cell disorder Clinical features
characterised by:
309
mebooksfree.com
Chronic phase Accelerated phase Blast crisis

Clinical Fever, night sweats, weakness, left Fever, night sweats, weight Fever, weight loss, easy
features upper quadrant pain, bone pain, loss bruisability, pruritus and
pallor, hepatosplenomegaly urticaria(due to basophilia)
Lab findings Anemia—normocytic normochromic Anemia Anemia
Leucocytosis—8000–800,000/mm3 Leucocytosis Leucocytosis
Thrombocytosis Thrombocytosis/ Thrombocytopenia
Peripheral smear—myeloid cells thrombocytopenia Immature cells with blasts
at all stages High proportion of in PS
Uric acid—may be elevated immature cells in PS Elevated uric acid
LDH—increased Elevated uric acid Elevated LDH
Bone marrow: hypercellular with Elevated LDH Hypercellular, basophilia
granulocyte hyperplasia, eosinophilia, Hypercellular, basophilia, with myeloblasts
basophilia and increased increase in blasts in bone
megakaryocytes, blasts < 10% marrow
Cytpgenetics T(9;22)fusion Duplication of Ph1 Clonal elevation
chromosome
Trisomy 8
Trisomy 19
Complications Epidemiology
• Metabolic disorders—hyperuricemia/hyperkalemia/ • 7% of childhood cancer
hyperphosphatemia • Affects ages 15–19 years
• Hyperleukocytosis • Male predominance <15 years.
• Thrombocytosis • Predisposing factors: immune deficiency,
• Priapism autoimmune disorders, human oncogenic viruses
• Meningeal leukemia (cytomegalovirus, Epstein-Barr virus).
• Differential diagnosis— Classification:
j Leukemoid reactions • 2 types:
j Juvenile myelomonocytic leukemia j Histopathological classification of classical
Management Hodgkin lymphoma
Principles j Modified Ann Arbor classification
• To achieve a cytoreduction by:
• Hydroxyurea: 25–50mg/m2/day based on Histopathological classification of classical Hodgkin
hematological response, achieves cytoreduction. lymphoma:
j Tumor lysis and hyperleukocytosis needs to be WHO Distinctive features
addressed subgroup
• Tyrosine kinase inhibitors—
Lymphocyte Lymphocytes with/without histiocytes
j Imatinib mesylate (1st generation TKI)—blocks
rich Few RS cells
the activity of BCR-ABL protein resulting in
No fibrosis
apoptosis. (340 mg/m2 as starting dose)
j Dasatinib/Nilotinib (2nd generation TKI) Nodular Thickened capsules dividing lymphoid
—80mg/m2 is well tolerated sclerosis tissue
Lacunar variant of RS cell
• Interferon-alpha: used in TKI intolerant patients.
• Stem Cell Transplantation: Mixed 5-15 RS cells/HPF
j Curative therapy. cellularity Fine fibrosis in interstitium
j Considered in suboptimal response/blast phase Focal necrosis
j Used in children failed in first line therapy or after Lymphocyte Abnormal cells is paucity of lymphocytes
cytoreduction with TKI depletion Fibrosis and necrosis
Modified Ann Arbor classification of Hodgkins lymphoma:

18.4 Hodgkin lymphoma
Stage Definitions
• Lymphoreticular malignancy I Single lymph node region or single
• Characterised by contiguous spread extranodal organ or site
310
mebooksfree.com
Stage Definitions
II Two or more lymph node regions
on same side of the diaphragm
or localised involvement of
extralymphatic organ
III Involvement of LN regions on both
sides of diaphragm with spleen
involved or localised involvement of
an extralymphatic organ
IV Noncontiguous involvement of one or
more extralymphatic site with/without
LN involvement
Annotations Definitions
A No B symptoms
B Unexplained weight loss >10% Figure 18.2 Reed Sternberg cell.
Unexplained persistant or recurrent
fever >38 degree celcius for 3 days
Drenching night sweats
X >6 cm mass > 1/3rd of mediastinal Treatment
diameter • Approach is early recognition of disease, monitoring
E Extension from contiguous nodal complications, recurrence and supportive care
disease to extralymphatic organ • Use of combined chemotherapy with or without low
dose field radiation
• Response to treatment is measured by PET scan
Etiopathogenesis
Chemotherapy regimens (28-day cycle)
• Cause is unknown
• First line therapy–ABVD regimen:
• 20%–50% classical HL have proliferation of EBV- doxorubicin (Adriamycin), bleomycin, vinblastine,
infected cells.
dacarbazine
• Reed-Sternberg (RS) cell is the hallmark of HL
• COPP/ABV: cyclophosphamide, vincristine
• Interaction between RS cell with inflammatory (oncovin), procarbazine, prednisolone, doxorubicin
cells, release of cytokine is important for
(Adriamycin), bleomycin, vinblastine
development of HL
• VAMP: vinblastine, doxorubicin (Adriamycin),
• Surface antigen expression includes CD30 methotrexate, prednisolone
Clinical Presentation • BEACOPP: bleomycin, etoposide, Adriamycin,
• Painless lymphadenopathy gradually increasing in cyclophosphamide, vincristine, prednisone,
size procarbazine.
• Cervical or supraclavicular lymphadenopathy Radiotherapy
• Anemia, neutropenia, thrombocytopenia
• Used in combination with chemotherapy
• Airway obstruction depends on extent of nodal
involvement
• Provides control for bulky disease, mediastinal mass
>1/3rd the thoracic diameter
• B symptoms- Fever, weight loss, drenching night
sweats Prognosis
Diagnosis & staging
• 5 year survival >90% regardless of stage
Investigations
• >90% for low-stage disease (stage I, II, non-bulky, no
B symptoms)
• Blood film – ESR elevated, increased serum ferritin
• 65%–90% for advanced disease (stage III, IV)
• Chest radiography – identifies the mediastinal mass
before lymph node biopsy
• Fluorodeoxyglucose Positron emission tomography
(PET) scan 18.5 Non-hodgkin leukemia
• CT scans of neck, chest, abdomen and pelvis describes
the extent of mediastinal mass • Arises from malignant proliferation of developing or
• Bone marrow aspiration and biopsy demonstrates mature B or T lymphocytes
moth-eaten nodular proliferation, Reed Sternberg • Extent of disease is determined using St Jude/
cells (Figure 18.2) Murphy’s staging system
311
mebooksfree.com
Epidemiology • B type symptoms: fever, night sweats, weight loss

• 3rd most common childhood malignancy • Infants have orbital involvement
• Male-to-female ratio: 3:1 Diagnosis & Staging
• Incidence increases with age (usually in 2nd decade • Bone marrow aspirate/biopsy: morphology of Burkitt
of life)
lymphoma
• Predisposing factors – immunosuppressive therapy, • Ascitic/pleural fluid for cytology
ionising radiation, Wiskott-Aldrich syndrome, viruses
(HIV, EBV), genetic syndromes (Bloom syndrome,
• FNAC of an enlarged lymph node
ataxia-telangiectasia) Lab Diagnosis
• Complete blood count
Classification • Evaluation of electrolyte imbalance
• Lactate dehydrogenase levels to estimate the risk
St. Jude staging system for childhood non-hodgkin group
lymphoma
• Potassium, calcium, phosphate, uric acid
Stage Description • Imaging: CT scan, PET scan, abdominal ultrasound,
MRI
Stage I Single tumor (extranodal) or single • CSF cytology
anatomical area (nodal), with exclusion of
mediastinum/abdomen Management
Stage 2 Single tumor(extranodal) with regional • Approach is diagnosis of the disease, prevention
and management of oncologic emergencies and
node involvement
2 or more nodal areas on same side of addressing their complications
diaphragm • Children with B-NHL treated with short, rapidly
2 single (extranodal) tumors with or repeated, pulse intense regimens.
without regional node involvement on Emergency management of
same side • Airway compression (SVC and esophagus) by
A primary GIT tumor with or without mediastinal masses.
mesenteric nodes >90% resected • Metabolic disturbances resulting in Tumor lysis
Stage 3 2 single tumors(extranodal) on opposite syndrome
sides • Massive serous effusions causing respiratory and
2 or more nodal areas above and below cardiac compromise
the diaphragm • Paraplegia from epidural tumors
Primary intrathoracic tumor • Obstructive jaundice and pancreatitis
Extensive primary intraabdominal disease • GI bleeding, perforation and bowel obstruction
Stage 4 Any of the above, with initial involvement
Treatment
of CNS or bone marrow at time of
diagnosis • Multiagent systemic chemotherapy with intrathecal
chemotherapy
• Duration:
Etiopathogenesis j Mature B-cell and ALCL – 1–8 months
• 4 subtypes j Lymphoblastic lymphomas – 24 months
j Lymphoblastic lymphoma (LBL) • Drugs: cyclophosphamide, vincristine, methotrexate,
j Burkitt lymphoma (BL) prednisone, dexamethasone, vinblastine,
j Diffuse large B-cell lymphoma (DLBCL) hydrocortisone
j Anaplastic large cell lymphoma (ALCL) • ALCL: crizotinib
• Immunodeficiency associated NHL usually of B cell • Immunotherapy:
origin j Rituximab
Clinical presentation j Brentuximab vedotin
• Systemic manifestations: Fever, weight loss, anorexia, • Surgery plays a limited role.
fatigue, less likely if tumor is localised Mature B-cell Complications
lymphomas • Tumour lysis syndrome
• Mediastinal mass symptoms: cough, hoarseness, • GI obstruction, bleeding, perforation
dysnea, chest pain • Inferior vena cava obstruction
• Marrow involvement: bleeding, bruising, bone pain • Neurologic complications (paraplegia, increased ICT)
• Tender or painless swelling in neck, axilla, groin or • Massive pleural effusion
extremities • SVC syndrome
• Painless swelling in neck, axilla, groin • Cardiac tamponade and arrhythmia
312
mebooksfree.com
Prognosis • Progresses to metastatic disease and death > 50%

• Favourable outcome in stages I and II with primary cases
site head and neck Clinical Features:
• Less favourable in stages III or IV, parameningeal
stage II, stage IV with CNS involvement Heritable Sporadic
• Incomplete remission within 2 months (50%–80% Retinoblastoma – 40% Retinoblastoma – 60%
survival) is least favourable. • Bilateral • Unilateral
• Multifocal • Non-transmissible
• RB1 gene mutations • No increased risk
also increases risk of to other non-ocular
18.6 Retinoblastoma osteosarcoma, soft tumors.
tissue sarcomas and
• Rare embryonal tumour of retina. This is the most malignant melanoma
common primary intraocular tumor and most
common inheritable tumor during entire childhood. Clinical features
• Median age at presentation is 2 years with >90% • White pupillary reflex is the most common
cases occurring before 5 years. presentation (Leukocoria; Amaurotic cat’s eye reflex)
• Incidence is 1:20,000 live births. (Fig. 18.3)
• Two thirds of cases have unilateral presentation. • Strabismus (Earliest presentation)
Bilateral involvement is common in cases presenting • Cataract, Poor vision
< 1 year • Proptosis associated bone pain
j 90% occurs sporadically • Rubeosis iridis, Heterochromia iridis
j 10%- familial (autosomal dominant) • Hyphema (blood in anterior chamber)
• Risk factors: • Secondary glaucoma
j Advanced paternal age • Aseptic orbital cellulitis
j In-vitro fertilization • Pseudohypopyon
j UV light exposure • Metastasis:
j Radiation exposure during early pregnancy j Local spread to vitreous, aqueous and choroid.
Etiopathology j Along optic nerve to brain
• The retinoblastoma gene is located on chromosome j Most common secondary malignancy is osteogenic
13 and encodes retinoblastoma protein. This protein sarcoma
binds to histone deacetylase causing silencing j Though metastasis is relatively uncommon it
of transcription. Mutation of this gene (13q 14 occurs predominantly in liver
deletion) also carries a risk of osteosarcoma and • Diagnosis:
pineal tumor. Obeys Kundson’s two-hit hypothesis. j This tumor doesn’t need biopsy or FNAC for
• Multicentric origin of retinoblastoma is characteristic diagnosis.
• 3 common growth pattern are observed: j Diagnosis is based on clinicoradiological pictures.
j Intraretinal (growth only in the retina) j Sensitive and diagnostic test – CT scan
j Endophytic (inner surface of retina to vitreous) j Enzyme markers: LDH, CEA
j Exophytic (outer surface of retina to subretinal
space)
• Invasion of optic nerve and massive choroidal
invasion is a high risk feature
• Trilateral retinoblastoma: Bilateral retinoblastoma
with pineal gland involvement
• Histology
j Flexner-Wintersteiner Rosettes-True rosettes
j Homer-Wright Rosettes
j Pseudorosettes
j Fleurettes
j Calcification
• Enzyme marker- Increasing LDH and
phosphoglucoisomerase
• High prevalence of retinoblastoma is seen in trisomy 21.
• Most commonly used staging system- Reese-
Ellsworth classification. Figure 18.3 Leukocoria.
313
mebooksfree.com
Approach and management • It is commonly seen in early childhood with >90%

• Clinical examination: visual acuity, slit-lamp or cases occurring in less than 5 years.
ophthalmic examination • Common sites include adrenal medulla (40%),
• Anterior segment examination – hyphema, rubeosis paravertebral region of abdomen (25%), posterior
iridis, iris nodules, corneal edema mediastinum (15%) and pelvis (5%)
• Posterior segment examination – mass exophytic, Pathology:
endophytic or mixed, retinal detachment
• Autosomal dominant transmission in some cases
• Intraocular pressure and corneal diameter measurement • Rearrangement or deletion of short arm of
• RetCam imaging – retinoblastoma documentation chromosome 1 seen in >80% cases
and monitoring response to treatment
• Associated with mutations of N-MYC,
• CT scan < 3 years and MRI > 3 years of age. hyperdiploidy, loss of heterozygosity of 1p, 11q,
Differential Diagnosis 14q and gain of 17q
• Congenital cataract – opacification of the lens • High frequency of spontaneous regression.
• Coats disease- Subretinal fluid and lipid accumulation Clinical Features:
• Persistent hyperplastic vitreous – remnants of • Clinical features are related to involved organs, extent
embryonic mesenchymal tissue in vitreous cavity and metastasis
• Retinal detachment – Fluid under retina • Asymptomatic and incidental finding of paraspinal,
• Retinopathy of prematurity – Abnormal retinal localized retroperitoneal or intrathoracic mass have
development been commonly reported.
• Toxocariasis – chorioretinal scarring and vitreous • Abdominal masses often cross midline and displace
inflammation, granulomas the kidney downwards without compressing
Management collecting system.
• Treatment aims at complete cure, preserving • Infants often present with subcutaneous tumour
vision, management and prevention of secondary nodules, massive liver involvement, bone marrow
malignancies disease and without bone involvement
• Primary Enucleation in unilateral disease (Less • Common presenting features include orbital
preferred option these days) proptosis (Figure 18.4), Raccoon eyes, bone pain
• Laser photocoagulation or cryotherapy (focal therapy) and fever. Bony involvement is characterised by lytic
in bilateral condition lesions in skull with sutural diastasis, spinal cord
• External-beam irradiation for large tumors compression
• Brachytherapy or episcleral plaque radiotherapy is an • Involvement of superior cervical ganglion presents
alternative with Horner syndrome.
• Systemic Chemotherapy – Carboplatin, Vincristine & • Catecholamines released by the tumour can cause
Etoposide tachycardia, headache, sweating, episodic diarrhea
and flushing
Unilateral disease Enulceation • Localized disease presents as asymptomatic mass,
superior vena cava syndrome, bowel obstruction and
Bilateral disease Chemoreduction with Focal
spinal cord compression
laser photocoagulation/
cryotherapy – First line • Metastatic disease presents with fever, irritability,
Enucelation and irradiation of bone pain, failure to thrive, cytopenias, bluish
other eye (Less preferred)
Prognosis
• 95% curative
• Trilateral retinoblastoma carries high mortality
• RB1 mutations have risk to develop secondary
malignancies
18.7 Neuroblastoma
• Most common intra-abdominal tumor in children

and commonest tumor of infancy
• It is a malignant tumor of autonomic nervous system
derived from primordial neural crest cells. Figure 18.4 Proptosis seen in Neuroblastoma.
314
mebooksfree.com
subcutaneous nodules, orbital proptosis and

periorbital ecchymoses. Multiple cutaneous Stage Definition
metastases can present (Blueberry muffin syndrome) 4 Any primary tumor with dissemination to
• Commonest site of metastasis is skeletal system. distant lymph nodes; bone, bone marrow,
Other sites of metastasis include liver, lymph nodes liver, skin, and other organs (except as defined
and skin. Lung metastasis is uncommon. Encasement for stage 4S)
of abdominal aorta and IVC may occur 4S Localized primary tumor in infants < 1 year,
Diagnosis with dissemination limited to skin, liver,
• Histopathology and bone marrow (limited to infants < 1 year
j Based on the tumour cell morphology, of age)
neuroblastoma is classified along with
‘Small round blue cell tumor. HPE shows central
space filled with eosinophilic fibrillary material Treatment:
surrounded by concentrically arranged tumor cells • Standard treatment modalities include chemotherapy,
(Horner-Wright pseudorosettes) surgery and radiation therapy based on the stage of
j Electron microscopy shows central dense cores neuroblastoma
(containing catecholamines) surrounded by • Neuroblastoma stages 1 and 2 can be treated with
peripheral halo surgery alone and have the best prognosis
• Imaging • Surgery along with chemoradiation is done for
j Plain radiographs reveal stippled calcification advanced stages 3 and 4.
j Ultrasound to evaluate abdominal mass, organ • Common chemotherapy regimens used are
involvement and calcification j OPEC (Vincristine, Cyclophosphamide,
j Computed tomography - Used to assess extent of Cisplatinum, teniposide)
disease, calcification and haemorrhage. j CADO (vincristine, cyclophosphamide,
j MRI used to assess paraspinal tumours and spinal Doxorubicin)
cord compression • Most cases with Stage 4S resolve spontaneously
j Bone Scan (123I, 131I MIBG) for metastasis Complications
• Others • Growth delay, Renal insufficiency
j Blood counts, Bone marrow aspiration and biopsy • Hearing loss, Hypothyroidism
j Tumor markers: Elevated catecholamine metabolites • Recurrence and Second malignancy
like homovanillic acid & vanillyl mandelic acid • Cardiac dysfunction, Infertility
(VMA), Neuron-specific enolase (NSE) and ferritin Prognosis
International Neuroblastoma Staging system
• Age and staging are two most important prognostic
factors
Stage Definition • Low-risk disease > 90% survival
• Intermediate risk: 85% survival
1 Localized tumor restricted to site of • High-risk: 30%–50% survival
origin. Complete gross excision; ipsilateral
lymph nodes negative for tumor
microscopically Prognostic Factors in Neuroblastoma:
2A Localized tumor with incomplete gross
Good prognostic Factors Bad Prognostic Factors
excision; ipsilateral
Nonadherent lymph nodes negative for tumor • Age < 1 year • Age> 1 year
microscopically • Stages I and II • Stage III and IV
2B Localized tumor with or without complete • Hyperdiploidy or • Near diploid tumor
gross excision, ipsilateral nonadherent Triploidy • Trk B expression
lymph nodes positive for tumor; enlarged • Expression of Trk A gene • Deletion of
contralateral lymph nodes must be negative • Evidence of Schwanjian chromosome
microscopically stroma and gangliocytic 1 and 11
differentiation • Amplification of
3 Unresectable unilateral tumor infiltrating across
• Mitosis-Karryorrhexis N-MYC
the midline, with or without regional lymph
index <200/5000 cells • Telomerase
node involvement; or localized unilateral
expression
tumor with contralateral regional lymph
• Mitosis-Karyorrhexis
node involvement; or midline tumor with
Index> 200/5000
bilateral extension by infiltration (resectable)
cells
or by lymph node involvement
315
mebooksfree.com
j Fluorodeoxyglucose PET—for accurate staging

18.8 Rhabdomyosarcoma j Molecular genetics—Detection of fusion
transcripts (PAX-FOX1)
• Most common soft tissue sarcoma in children. It • Treatment:
originates from primitive mesenchymal tissue. j Primary treatment modality is surgery. Wide-local
• Bimodal age distribution is seen. First peak excision of tumor is performed if feasible.
is seen before 5 years and the next between j Neoadjuvant chemotherapy is given for tumors
15–19 years. not amenable to primary excision. This typically
• In first peak, head, neck, bladder and vagina involves chemotherapy induced tumour reduction
are involved. Second peak typically involves followed by surgery
genitourinary tract. j Radiation therapy is given when microscopic
• Seen in association with Neurofibromatosis, or gross residual disease exists after initial
Beckwith-Weideman syndrome, Li-Fraumeni treatment
syndrome and fetal alcohol syndrome. • Prognosis:
• Histological types—4 types are described j Prognosis is related to the site of origin, resectability,
j Embryonal type (60%) presence of metastases, number of metastatic sites, and
– Intermediate prognosis histopathologic features
j Botryoid type— j Involvement of vagina, testis and head and neck
– Common in childhood regions have favourable outcome
– Tumor cells and edematous stroma project into j Embryonal variant is a favorable and alveolar type
body cavities like Bunch of grapes has an unfavorable prognosis
– Commonly involves Uterus, vagina, bladder,
middle ear, and nasopharynx
j Alveolar type—(25%–40%)
– Presence of PAX/FOXO 1 fusion transcript 18.9 Brain tumors
– Tumour cells grow in nests and have cleft like
spaces resembling alveoli. 18.9.1 Astrocytoma
– Commonly involves trunk and extremities
– Worst prognosis. • Accounts for 40% of CNS tumours in children
j Pleomorphic type— • WHO classification types
– Adult form j Low-grade
– Rare in childhood – Grade I- Pilocytic astrocytoma, SeGA-
• Clinical features: subependymal giant cell astrocytoma
j Most common presentation is presence of mass. – Grade II- Diffuse astrocytoma
j Clinical symptoms are based on site of j High Grade
involvement – Grade III- Anaplastic astrocytoma
– Head and neck (25%)—Proptosis, nasal – Grade IV- Glioblastoma multiforme
obstruction, bloody nasal discharge Pilocytic astrocytoma:
– Genitourinary tract (22%)—Dysuria, • Most common site of involvement is cerebellum
Hematuria, Urinary obstruction followed by hypothalamus, third ventricle and optic
– Other sites: Orbit, Extremities, retroperitoneal, chiasma
perianal, GIT, and Prostate. • Ataxia and incoordination more on the sides of the
j Common sites of metastasis includes lung and lesion.
bone marrow • Nystagmus, areflexia, hypotonia.
• Investigation • MRI is the investigation of choice. Characteristic
j CT/MRI—to evaluate the primary tumor site feature seen is ‘contrast medium enhancing nodule’
j Histopathology within the wall of a cystic mass
– Microscopy reveals small, round, blue cell tumor • Microscopy- Presence of Rosenthal fibers, which are
– Diagnostic cell is rhabdomyoblast (contains condensed masses of glial filaments.
eccentric eosinophilic granular cytoplasm rich • Cerebellar astrocytoma is the most common
thick and thin fragments) —elongated tadpole posterior fossa tumor of childhood and has the best
or strape cells prognosis.
– Rhabdomyoblasts are positive for Desmin, • Management
MYOD1 and Myogenin j Current accepted modality for Low grade
j Radionuclide bone scan, CT thorax, bone marrow astrocytomas is primary surgery along with
aspiration and biopsy for metastasis chemoradiation
316
mebooksfree.com
18.9.2 Medulloblastoma • Tumour arises from remnants of craniopharyngeal

duct and Rathke’s pouch.
• Accounts for 90% of embryonal tumors • Adamantinomatous variant predominates in
• Peak age of occurrence is 5–7 years childhood
• Males are commonly affected than females • Clinical features-
Pathology j Commonly presents with endocrine abnormalities
• Most common site of involvement is midline (Growth failure, Delayed sexual maturation)
cerebellar vermis. In older patients, cerebellar j Visual disturbances (Bitemporal hemianopia,
hemispheres are involved. Visual field defect)
• Most common genetic aberration seen is the loss j Raised intracranial pressure.
of material from 17p. Others associated are MYC • Most common endocrinopathy - Reduced GH
amplification, increased neurotropin receptor TRKC secretion resulting in dwarfism
and nuclear accumulation of β- catenin • Adults commonly present with visual loss and
Clinical features endocrine dysfunction
• Patients present with features of raised intracranial • Diagnosis
pressure and cerebellar involvement j Xray: Ballooning of Sella
• Common presenting symptoms include headache, j CT scan: Suprasellar calcification is seen in 90%
vomiting, altered consciousness and hypertension j MRI can reveal solid tumor with fluid containing
suggestive of raised ICP. cystic structures within
• Cerebellar involvement presents with truncal • Treatment
ataxia, unsteadiness, in-coordination and broad j Tumour is mostly benign
based gait. Obstruction of fourth ventricle results in j Surgery is the mainstay of treatment. Gross total
hydrocephalus. resection is curative with small lesions
• Papilledema occurs very early in the course j Transcranial/ Trans sphenoidal surgical resection is
• Associated with nevoid basal cell carcinoma and the commonly performed surgery
Turcot syndrome j Occasionally surgical excision along with
• Dissemination through CSF is common resulting in hormonal therapy or surgical drainage of cyst with
nodular masses in CNS and metastases to Cauda equina radiotherapy is tried.
(Drop metastases)
Investigations
• Histology: Small round blue cell tumour, Homer
Wright rosettes 18.10 Childhood histiocytosis
• Computed tomography and MRI: Solid, homogenous,
contrast enhancing mass in posterior fossa • Rare and diverse group of disorders characterized by
• Immunopositivity for synaptophysin infiltration and accumulation of histiocytes in various
Treatment parts of the body.
• Current recommended approach is Multimodal Classification of Histiocytosis
treatment involving Surgery followed by Disorder of • Langerhans cell histiocytosis
chemoradiation. Dendritic (Histiocytosis X)
j Maximal surgical resection cells j Hand-Schuller-Christian
j Postoperative craniospinal irradiation disease
j Multi-agent chemotherapy – Cisplatin, Lomustine, j Letterer-Siwe disease
Cyclophosphamide & vincristine j Eosinophilic granuloma.
Prognosis - Poor • Juvenile Xanthogranuloma

• Solitary histiocytoma
• Good factors - β- catenin & increased neurotropin
receptor TRKC Disorder of • Hemophagocytic
• Bad factors–Loss of 17p and MYC amplification Macrophages Lymphohistiocytoses (HLH)
j Familial hemophagoytic lym-
phohistiocytosis
18.9.3 Craniopharyngioma j Associated with albinism
syndromes
• Most common supratentorial tumor in children • Rosai-Dorfman disease
• Age distribution is typically bimodal. First peak is Malignant • Acute Monocytic leukemia
seen between 5–10 years followed by another peak histiocytosis • Histiocytic sarcoma
between 50–60 years.
317
mebooksfree.com
18.10.1 Langerhans cell • Gingival mucous infiltrative lesions

histiocytosis (LCH) • Pituitary dysfunction or hypothalamic involvement
may result in
• Rare, unpredictable, non-malignant disease j Growth retardation
characterized by proliferation of Langerhan j Diabetes insipidus
histiocytes (tissue macrophages) in tissues. j Secondary hypothyroidism
• Clinical presentation and organ involvement j Panhypopituitarism
is variable ranging from mild single system • Central nervous system (CNS) involvement
involvement to life threatening multisystem characterized by
disease j Ataxia
• Reactive production of dendritic cells j Dysarthria
Clinical types: Diagnosis:
• Eosinophilic granuloma • Tumour Markers: S-100, CD 1a, HLA DR, Langerin
j Chronic unifocal LCH of bone (CD 207)
j Solitary calvarial lesion in young adults. • Radiologic features - Multiple well-defined lytic
j Common sites involved are skull, ribs, femur, bony lesions, Geographic skull, Vertebra plana
pelvis and spine. (vertebral destruction and vertebral collapse),
j Associated features include otitis media, proptosis, Floating teeth
pituitary dysfunction and spontaneous fractures • Electron microscopy reveals presence of the
• Hand Schuller Christian disease characteristic Birbeck granules in the cytoplasm.
j Classic multifocal LCH These granules have a pentalaminar, rod like, tubular
j Triad of Diabetes insipidus, Exophthalmos and appearance and a dilated terminal end giving rise to
Bony defects Tennis racket appearance
• Letterer-Siwe disease • Urine osmolality
j Acute, severe disseminated form of LCH
Treatment:
j Cutaneous lesions in scalp, face, trunk and buttock
mimicking seborrheic dermatitis
• Treatment depends on systems involved and the
extent of involvement.
j Fever, anemia, thrombocytopenia, pulmonary
infiltrates
• For localised disease, observation, steroids,
indomethacin, curettage, low dose chemotherapy or
j Spleen and liver enlargement,
local radiation therapy are tried
Lymphadenopathy
• For Multisystem disease, systemic combination
Clinical Features chemotherapy (vinblastine, 6 mercapto-purine and
• Skeletal Involvement (80%) steroids) is the standard treatment. For resistant
j Seen in Children older than 5 years cases, cyclosporine/antithymocyte globulin, Imatinib,
j Osteolytic lesions with sharp borders occur in flat Cladribine and Stem cell transplantation are other
and long bones alternatives.
j No evidence of reactive new bone formation
j Risk of pathological fracture
Destruction in the mastoid area produce
j
chronically draining, infected ears

18.11 Wilms tumor
j Destruction of mandible and maxilla leads to free
floating teeth in radiography. • Wilms tumor (Nephroblastoma) is the most
• Skin involvement (50%) common primary malignant renal tumor of
j Seborrheic dermatitis of the scalp or diaper childhood, accounting for 6%–7% of childhood
region. malignancies
j The exanthem may be petechial or hemorrhagic, • Second common malignant abdominal tumor in
even in the absence of thrombocytopenia. childhood following neuroblastoma
• Systemic manifestations • Most cases are diagnosed between 2-5 years
j Fever, weight loss, malaise, irritability, and failure • Both sexes are affected equally
to thrive. • About 10% of the tumors are bilateral or multicentric.
j Localized or disseminated lymphadenopathy in • Most of the tumors are sporadic while 1%–2% may
33% patients. be familial
j Hepatosplenomegaly in 20% patients. • Familial cases may follow autosomal dominant
• Exophthalmos, caused by retro-orbital accumulation inheritance and are often bilateral
of granulomatous tissue. Etiology - Mutation of following genes
318
mebooksfree.com
j Wilms tumor gene (WT1) on chromosome 11p13 Hypertension is commonly present at diagnosis and
which encodes a transcription factor regulating might persist till nephrectomy.
normal development of urogenital system. • Other features include
j WT2 gene on chromosome 11p15 j Anemia, polycythemia, thrombocytosis
j CTNNB1 gene (encoding β-catenin) and p53 j Acquired deficiency of von Willebrand factor and
gene factor VII
• Syndromes associated with Wilms tumor: Differential diagnosis:
A) WAGR syndrome • Neuroblastoma
– Del11p12(WT1 and PAX6) • Hydronephrosis
– Wilms tumor, Aniridia • Multicystic kidney
– Genitourinary abnormalities • Abdominal lymphoma
– Mental Retardation • Retroperitoneal rhabdomyosarcoma
B) Denys-Drash syndrome
Diagnosis:
– WT1 missense mutation
– Early onset renal failure with renal mesangial • Abdominal ultrasound is the most important
investigation which will differentiate solid from
sclerosis
cystic masses.
– Gonadal dysgenesis (Male
pseudohermaphrodism) • CT and MRI is primarily used know the extent/staging
of disease and to rule out tumour in contralateral
– Gonadoblastoma
kidney.
C) Beckwith Wiedemann syndrome
– Genomic imprinting (Unilateral paternal • Lesions can be calcified. It is usually crescent shaped,
discrete and peripheral
disomy, duplication of 11p15)
– Microdeletions within the IGF2 imprinting • Biopsy is a reliable diagnostic tool, but results in
disease upstaging.
control region.
– Somatic overgrowth syndrome • Xray chest to rule out lung metastasis
– Predisposition to embryonal tumors Staging:
– Hemihypertrophy, Macroglossia • Stage I – Tumor confined to kidney and completely
– Organomegaly, Omphalocele excised
– Abnormal large cells in adrenal cortex (Adrenal • Stage II – Tumor extends beyond the kidney but still
cytomegaly) completely excised
Histology: • Stage III – Residual non hematogenous tumor
confined to abdomen after resection positive lymph
• Nephrogenic rests are the presumed precursor node and tumor spillage
lesions of Wilms tumor and are seen in the adjacent
renal parenchyma • Stage IV – Hematogenous metastases to lung or
liver
• Tumour contains three elements – Blastema,
Mesenchyme and epithelium • Stage V – Bilateral renal involvement at diagnosis
Treatment:
Favorable histology Unfavorable histology • Management of Wilms tumor is based on staging and
histological type
• Comprises of • Marked enlargement
blastema, epithe- of nuclei • Current accepted guideline is complete surgical
lial and stromal • Hyperchromatism resection of unilateral affected kidney along with
elements. and multipolar peri-operative chemo and radiotherapy.
• Devoid of anapla- mitotic figures • Vincristine, Actinomycin D and adriamycin are
sia or ectopia. • Anaplasia is present commonly used for chemotherapy.
• Brain and bone • Clear cell Sarcoma is • Radiotherapy should be started within 10 days after
metastasis is rare. a subtype and usually nephrectomy in unfavorable histology
• Metastasis may metastasizes to bone. • Pulmonary irradiation is given in cases of lung
involve lung metastasis
Clinical Features: Stages Treatment

• Asymptomatic abdominal mass palpated during I and II Surgery + Chemotherapy (Vincristine
bathing or routine examination is the most common & Dactinomycin)
presentation. The classic clinical triad of symptoms
III Surgery + Chemotherapy (Vincristine,
include abdominal mass, fever and hematuria.
Dactinomycin & Doxorubicin)
Occasionally children present with anorexia poor
radiotherapy to tumor bed
appetite, recurrent vomiting and failure to thrive.
319
mebooksfree.com
Stages Treatment Poor prognostic factors Good prognostic factors

IV Surgery + Chemotherapy (Vincristine, • Unfavorable • Young age
Dactinomycin & Doxorubicin) histological type • Early stages (I & II)
radiotherapy to all sites • Larger tumor • Low tumor weight
Unfavorable Surgery + Chemotherapy (> 500 gms) (<550 g)
histology (Vincristine, Dactinomycin, • Hyperploidy
Doxorubicin & cyclophosphamide) + • Advanced stages
radiotherapy (III & IV)
Prognosis
• With current combined therapy, cures rates upto Online supplementary materials:
80%–90% can be reached. Please visit MedEnact to access chapter wise MCQs and
• Presence of anaplasia, loss of heterozygosity of 1p or
16 q increases the risk for recurrence final MBBS University examinations.
320
mebooksfree.com
Chapter | 19 |
Dermatology
• Acrocyanosis is not associated with edema or other

19.1 Skin physiology cutaneous changes.
• Commonly seen immediately after birth and can
• Skin functions as a protective barrier preventing persist for few days.
infections, facilitates thermoregulation and helps • Due to benign vasomotor changes causing peripheral
to control insensible water loss and electrolyte vasoconstriction and exaggerated oxygen extraction by
balance. Neonatal skin is less hairy, has less sweat and tissues
sebaceous gland secretions when compared with adult • This is a benign and self-limiting. Requires no therapy.
skin. It is relatively thinner, has fewer intercellular
attachments and melanosomes. The general structural 19.2.2 Cutis marmorata
development of skin is completed by 24 weeks of
gestation, but epidermal barrier function is immature
• Characterized by reticulated appearance or marbling
of the skin (Fig. 19.2)
until after birth. Complete maturation typically takes
2 to 4 weeks of postnatal life.
• Lacy, reticulated vascular pattern over body
• Associated with cold stress and hypothermia
• The epidermis is composed primarily of keratinocytes, • Symmetrical involvement of the trunk and
which matures to form stratum corneum. The dermis
extremities.
is made up of collagen and elastin fibres. These
fibres provide elasticity and connect the dermis to
• Benign self-limiting condition. Disappears
spontaneously during neonatal period
the epidermis. Dermis also contains abundant blood
vessels, nerves, sweat glands and hair follicles. The
• Persistence beyond neonatal period may indicate
j Trisomies: Down’s syndrome & Edward syndrome
fatty connective tissue in subcutaneous layer provides
j Cornelia de Lange syndrome
insulation and protection.
j Hypothyroidism
• The preterm babies born <30 weeks have 2 to 3
layers of stratum corneum less when compared with
the normal 10 to 20 layers seen in term newborns. 19.2.3 Harlequin color change
However, after birth there is accelerated maturation of • Etiology unknown
stratum corneum in 2 weeks after preterm birth. • Occurs due to vasomotor instability
• When the infant is placed horizontally, the dependent
half of the body becomes bright red when compared
with the pale upper-half. Some cases can demonstrate
19.2 Benign skin lesions shifting of colours when the infant is rolled to the
in newborn other side.
• There is a sharp demarcation of blanching (one side
of the body is red and the other is pale)
19.2.1 Acrocyanosis
• This phenomenon is transient and usually lasts from
• The palms and soles become variably and few seconds to 20 minutes
symmetrically blue in color (Fig. 19.1) • Recurrences are common until 3–4 weeks of life.
321
mebooksfree.com
Figure 19.1 Acrocyanosis.

Figure 19.3 Erythema toxicum neonatorum.
• Discrete red or hemorrhagic nodules and plaques up

to 3 cm in diameter
• Lesions commonly seen in areas exposed to trauma
• Commonly seen in cheeks, back, buttocks, arms and
thighs, during the first few weeks of life.
• The lesions occasionally become fluctuant, drain and
heal with atrophy
• Lesions are usually painless, occasionally tenderness
may be present
• Risk factors
Difficult deliveries
j
Hypothermia
j
j Perinatal asphyxia
Figure 19.2 Cutis marmorata.
j Maternal diabetes
• Histopathology demonstrates necrosis of fat with a
foreign body giant cell reaction. Remaining fat cells
19.2.4 Erythema toxicum
contain needle-shaped clefts, and calcium deposits
neonatorum (ETN) are scattered throughout the subcutaneous tissue
• Commonly seen in term infant (70%) • Nodules usually resolve without scarring in 1–2 months.
• Usually appears on the second or third day of life
• Erythematous, blotchy macules and papules of 19.2.6 Mongolian spots
2–3 mm diameter
• Lesions evolve into pustules on a broad erythematous • Consists of grey blue macules presenting in
base to give characteristic a “flea-bitten” appearance lumbosacral region (Fig. 19.4)
(Fig. 19.3) • Commonly seen at birth in Asian infants.
• Lesions may be isolated or clustered on the face, • It is due to ectopic melanocytes in dermis.
trunk and proximal extremities, and usually fade over • Benign and self-limiting condition
5–7 days • Disappears spontaneously by 6 months to 2 years.
• New crops of lesions can appear after the initial onset • Extensive spots seen in GM1 gangliosidosis,
• Laboratory investigations: Mucopolysaccharidoses
j Eosinophilia in 15–20% cases Sebaceous Gland Hyperplasia
j Wright’s stain of pustule shows sheets of • Commonly found over the nose and cheeks of term
eosinophils and occasional neutrophils. infants
• This condition is benign and self-limiting.
19.2.7 Miliaria
19.2.5 Subcutaneous fat necrosis
of the newborn • Occurs frequently in term and rarely in preterm infants
after the first week of life in response to thermal stress
• Rare condition seen in healthy full-term and post- • Miliaria results from obstruction to the flow of sweat
mature infants. and rupture of the eccrine sweat duct
322
mebooksfree.com
Dermatology Chapter | 19 |
Figure 19.5 Miliaria crystallina.
j Miliaria profunda: Deep-seated papulopustular

lesions; Duct ruptures at the dermal-epidermal
junction
Figure 19.4 Mongolian spots. 19.2.8 Milia

• The lesions are pearly, whitish yellow, pin head sized
• Eruption occurs in crops in the intertriginous areas, papular lesions of 1–3 mm diameter (Fig. 19.6A)
scalp, face and trunk. • Commonly seen in the face, chin and forehead
• In older infants, lesions appear most commonly in • Caused by sebaceous retention cysts
areas of skin occluded by tight-fitting clothing. • Histology reveals miniature epidermal inclusion cysts
• The following types of miliaria occur in the neonate: that arise from the pilosebaceous apparatus of vellus
j Miliaria crystallina: Superficial, 1–2 mm diameter hairs
vesicles appear on non-inflamed skin when the • Milia usually spontaneously resolve within 2–3 weeks.
duct is blocked by keratinous debris just beneath • Milia when present in gum margin is known as
the stratum corneum (Fig. 19.5). Lesions mimick Bohn nodules and Epstein pearls (Fig. 19.6B) when
sprinked water droplets present in midline palate
j Miliaria rubra (Prickly heat): Small papules and • Oral-facial-digital syndrome or hereditary
pustules develop due to the obstruction in the mid trichodysplasia (Marie Unna hypotrichosis) should
epidermis be considered if lesions persist during infancy.
Figure 19.6 A, Milia. B, Epstein’s pearls.

323
mebooksfree.com
19.3 Scabies 19.4 Pediculosis
Etiology: Etiology:
• Scabies is caused by Sarcoptes scabei var hominis • Pediculosis humanus (P. humanus capitis – head louse,
Mode of Transmission: P. humanus corporis- body louse)
• By close contact with infested humans • Phthirus pubis (pubic louse)
Clinical features: Mode of Transmision:
• Severe itching, more at night. • Head louse infestation is acquired by close contact
• Primary lesion is burrow-a grey thread like serpentine • Pubic louse infestation is acquired by children from
line with a minute papule at the end. Papule and infested parents
papulovesicles can also be seen (Fig. 19.7) • Head louse infestation is more common in children
• Secondary lesions – pustules, eczematized lesions and while pubic louse infestation is infrequent but when
nodules. it occurs also involves eyelashes and eye brows.
• Location – webs of hands, on wrists, ulnar aspects of Clinical Features:
forearms, elbows, axillae, umbilical area, genitalia, • Pruritis involving infested region is the chief symptom
feet and buttocks. • Adult lice are difficult to find but nits (egg-capsules)
• Face is usually spared except in infants in whom are easily seen firmly cemented to hair.
scalp, palms and soles are also involved. • Lesions may show secondary infection,
• Secondary streptococcal infection may result in acute eczematization and occipital lymphadenopathy
glomerulonephritis Treatment:
Treatment: • All family members should be treated
• Blanket therapy – All close contacts of the patient, • Permethrin 1% lotion, single 10 min application to wet
even if asymptomatic should be treated. hair followed by rinsing. Repeat application after 7 days
• Laundering of bed linen and clothes. • Gamma benzene hexachloride – 1% single overnight
• Scabicides available include: application to dry hair followed by rinsing. Second
j Permethrin 5%- overnight single application is the application after 7 days.
treatment of choice in >2yrs • Malathion 0.5% water based lotion, applied on dry
j Crotamiton 10% - Two application daily of hair for 6 hr. Secondary application not needed due
14 days for infants < 2months. to residual effect.
j Benzyl benzoate 25%- Three applications at 12 • For eyelash infestations – Petrolatum twice daily for
hourly intervals 7-10 days is used. Petrolatum covers the lice and their
• Ivermectin single dose of oral 200microgram/kg body nits, preventing their respiration. The dead lice are
weight, in children older than 5 years is the treatment removed mechanically with a pair of tweezers
of choice for epidemics.
• Antihistamine to reduce pruritis and antibiotics if
secondary infection is present.
19.5 Atopic dermatitis
• Atopic dermatitis is an acute, subacute or chronic

relapsing, endogenous eczema, characterized by dry skin
and pruritic, recurrent symmetric dermatitis lesions.
Clinical Features and Diagnosis
• In children, two distinct patterns of AD are seen.
• Infantile pattern:
j Onset in infancy after 3 months of age
j Itchy, erythematous papulovesicles seen on the face.
j The lesions clear by 18 months of age in 40% and
in the rest evolves into childhood pattern
• Childhood pattern:
j Characterized by lichenified and crusted plaques
j Seen in Antecubital fossa, popliteal fossa, neck
and face.
Figure 19.7 Scabies. j 70% clear by 10 years of age.
324
mebooksfree.com
Hannifin and Rajka’s criteria for atopic dermatitis
Major features (must have 3 or more) Minor features ( must have 3 or more)
• Pruritis • Cataracts (Anterior sub capsular) • Itching when sweating
• Typical morphology and distribution • Ichthyosis • Hand dermatitis
• Dermatitis chronic or chronically • Cheilitis • Keratoconus
relapsing. • Elevated levels of Ig E • Ichthyosis
• Personal or family history of atopy • Conjunctivitis, recurrent • Keratosis pillars
(asthma, allergic rhinitis, atopic • Immediate skin test reactivity • Palmar hyper linearity
dermatitis) • Facial pallor or erythema • Perifollicular accentuation
• Infections • Pityriasis alba
• Food intolerance • White dermographism
• Wool Intolerance
• Xerosis
Complications:
• Superimposed bacterial or viral (herpes simplex,
molluscum contagiosum) infections
• Infections: Bacterial(impetigo), viral (herpes,
molluscum) and fungal infections
• Disturbed sleep and poor growth.
Treatment:
• Acute eczema:
j Wet dressings, topical steroids and topical Figure 19.8 Molluscum contangiosum.
antibiotics if indicated.
j Oral antihistamines, Probiotics Dermatopathology:
• Chronic eczema: • Henderson Peterson bodies (molluscum bodies) are seen.
j Hydration followed by application of petrolatum
Treatment:
j Topical steroids + Keratolytic agent like salicylic
acid if lichenified
• Cryotherapy using liquid nitrogen (10-15 seconds)
j Topical immunomodulator like tacrolimus
• Simple mechanical methods like expression of the
contents of papule by squeezing it with a forceps held
j Oral antihistamines to break the ‘itch-scratch’ cycle.
parallel to the skin surface.
j Narrow band UVB, PUVA and cyclosporine are
useful in resistant cases
• Light electrocautery.
19.6 Molluscum contagiosum 19.7 Diaper dermatitis
Definition: Etiology:
• Molluscum contagiosum is due to infection with • An irritant dermatitis in infants caused by
poxvirus. prolonged contact with feces and ammonia released
from urine
• Incubation period is 14 days to 6 months.
• Lesions are produced by the action of urea splitting
Mode of Transmission: organisms on urine
• Direct contact or indirectly through fomites and towels.
Clinical Features:
Clinical Features:
• The area in contact with diapers shows moist, glazed
• Discrete pearly white colored hemispherical papule with erythematous lesions with sparing of flexures
smooth centre and umbilicated centre (Fig.19.8)
Prevention:
• White curd like substance can be expressed on
squeezing the fully developed lesions • Avoid use of disposable diapers
• Most of the lesions resolve spontaneously. During • Keeping area clean, dry.
involution there may be mild inflammation and • Rinsing washed cotton diapers well
tenderness. Treatment:
• Sites of Predilection: Face and eyelid, neck and • Emollients and mild topical steroids with anti fungal
forearm, trunk, axillae, anogenital areas and thighs. agents useful in acute phase.
325
mebooksfree.com
19.8 Pyoderma
• It is the bacterial infection of skin.

Classification
Clinical features of non-follicular pyoderma Clinical features of spreading pyoderma
Impetigo Bullous Erysipelas Cellulitis

contagiosa impetigo Ecthyma
Clinical Red, hot, edematous, Red, hot
Age Children Infants Any age features well defined rapidly edematous
Clinical Thin-walled Thick walled Crusted, spreading plaques rapidly spreading
features blisters on persistent tender with superficial ill defined, deep
erythema- blisters on erythe- vesiculation plaques
tous base. bland skin. matous
Rupture Rupture only indu-
rapidly to after a few rated
leave honey days to leave plaque. Clinical features of follicular pyoderma
colored thin varnish Heals
Folliculitis Furuncle
crusts. like crusts. with
Lesions Lesions heal scarring. Clinical Erythema- Firm red follicular
spread in centre features tous follicular nodules which
without to form papules often discharge pus and
central annular surrounded by heal with minimal
clearing. plaques. pustules scarring
Lymphad- Lymphad- Sites of Face, lower Buttock, lower
enopathy enopathy predilection extremities extremities
frequent rare.
Sites of Face, Face and Buttocks,
predilection especially other parts thighs Treatment:
around the of body and legs
• Topical antibiotics like mupirocin, sodium
mouth and
fusidate and nadifloxacin are used for localized
nose.
lesions.
Complica- PSGN SSSS PSGN • Patients with extensive spreading lesions require
tions Scarring Eczema- therapy with systemic antibiotics.
tization
• General measures include local hygiene, rest and limb
Scarring
elevation in case of spreading pyodermas.
326
mebooksfree.com
Treatment:
• General measures - avoiding friction and trauma
• Prompt and appropriate use of antibiotics
• The role of Vitamin E and phenytoin is doubtful
• Surgery may be required for release of fused digits,
correction of limb contractures and esophageal
strictures.
19.10 Steven johnson syndrome
• Immune-complex–mediated hypersensitivity
syndrome affecting skin and mucous membranes.
• Minor form of toxic epidermal necrolysis
• <10% of body surface area involved.
Etiology:
Figure 19.9 Lesions of Epidermolysis Bullosa. • Infection - Mycoplasma pneumoniae
• Drugs - NSAIDS, antibiotics, anticonvulsants
• Genetics - HLA B*1502 and HLA B*5801
Pathogenesis:
19.9 Epidermolysis bullosa
• Pathogenesis is related to drug specific CD8 cytotoxic
T cells with Perforin/granzyme triggering keratinocyte
• Heterogenous group of disorders characterized by apoptosis.
tendency to develop blisters even on trivial trauma Clinical features:
(Fig. 19.9). • Skin lesions plus two or more mucosal surface
Classification of EB: involvement
• Inherited EB: • Commonly involved mucosa includes eyes, oral
j EB simplex - Autosomal dominant; defective cavity, upper airway, GI mucosa and urogenital
keratin gene. mucosa (Fig. 19.10)
j Junctional EB - Autosomal recessive. • Typical rash starts as a macule but can progress into
j Dominant dystrophic EB - Autosomal dominant; papules, vesiculobullous or urticarial plaques.
defective collagen 7 gene • Presence of target lesions are pathognomonic
j Recessive dystrophic EB - autosomal recessive. Differential diagnosis:
• Acquired EB: • Toxic Epidermal Necrolysis
j EB acquisita - Immune mediated • Urticaria
Clinical features of Epidermolysis Bullosa:
Autosomal dominant Autosomal recessive

EB simplex Junctional EB dystrophic EB dystrophic EB
Age of onset Early childhood At birth At birth At birth
Skin lesions Non-hemorrhagic Large flaccid bulla Hemorrhagic blisters Hemorrhagic blisters
bulla develop on which heal slowly which heal with scaring which heal with
normal skin severe scarring
Sites Sites of repeated Perioral, perianal Sites of friction(knee, Generalized
trauma (hands and areas and sites of elbows, fingers)
foot) trauma
Mucosal lesion Mucosa spared Involved Minimal mucosal Severe mucosal
involvement involvement
Nail involvement - + + ++
Complications Heal without One variant is Scarring and milia Severe scarring
scarring lethal formation
327
mebooksfree.com
j Sudden onset and generalization within 24-48 hours.

j Histology finding of full thickness epidermal
necrosis and no dermal infiltrates
Clinical Manifestations:
• Fever, Malaise, diffuse erythema, inflammation of
eyelid, conjunctiva and mouth
• NIKOLSKY sign - denudation of skin with gentle
tangential pressure
• Scarring, particularly of eyes may lead to corneal
opacity.
• Course may be progressive complicated by severe
dehydration, electrolyte imbalance, shock and
secondary localized infection and septicemia.
Differential Diagnosis:
• SSSS
• GVHD
• Toxic shock syndrome
• Pemphigus
Treatment
• Withhold the offending drug
• Management is similar to severe burns and is best
done in burns unit.
• Systemic antibiotics in case of secondary infection.
Figure 19.10 Steven Johnson syndrome.
• Skin care - /Isotonic saline dressing. Biological or
colloid gel dressings alleviate pain and reduce fluid loss.
• Systemic corticosteroids and IVIG may be useful
• DRESS (Drug rash with eosinophilia and systemic
symptoms)
Treatment
19.12 Staphylococcal scalded skin
• Management of SJS is mainly symptomatic and syndrome
supportive.
• Potentially offending drugs must be discontinued • It is also known as Ritter’s disease.
• Ophthalmology consultation is mandatory as ocular Etiology:
sequelae like corneal scarring can lead to vision loss.
• Phage group 2 staphylococci, particularly strains 71
• Oral lesions - Mouth washes and glycerin swabs. and 55
• Vaginal lesions - observed carefully to prevent • Due to release of Epidermolytic toxin A and B
formation of strictures
• The site of blister cleavage is sub corneal and the blister
• Systemic antibiotics - for documented urinary and fluid is characteristically sterile unlike bullous impetigo.
cutaneous infections
• Corticosteroids can be used in early stage of the Clinical Manifestations:
disease. • Occurs predominantly in children less than 5 years
• IVIG (IV immunoglobulin) 1.5-2.0g/kg/day should • Scarlentiform erythema
be considered in early disease. • Conjunctiva - inflamed.
• Nikolsky sign positive - Areas of epidermis may
separate in response to gentle shear force.
• As large sheets of epidermis peel away, moist,
19.11 Toxic epidermal necrolysis glistening pale areas become evident.
• Secondary bacterial infection is common.
• Etiology: Hypersensitivity reactions to drugs like • Desquamative phase begins 2-5 days after erythema
sulfonamides, amoxycillin, phenobarbitone, and healing occurs without scarring in 20 to
allopurinol. 14 days.
• >30% of body surface area involved Differential diagnosis:
• Toxic Epidermal Necrolysis is defined by: • Bullous impetigo
Widespread blister formation.
j
• Drug eruption
Absence of target lesions.
j
• Toxic epidermal necrolysis
328
mebooksfree.com
Histology Treatment:
• Subcorneal blisters • Lifelong Oral therapy with zinc compounds is the
• Absence of inflammatory infiltrate is characteristic. treatment of choice.
Treatment: • Dose - zinc -50 to 150mg/day
• Penicillinase resistant penicillin
• Clindamycin is added to inhibit bacterial protein
synthesis
19.14 Ichthyosis
Complications:
• Excessive fluid loss and electrolyte imbalance
• Pneumonia, septicemia, cellulitis Definition:
• Recovery is usually rapid. • Ichthyosis vulgaris (autosomal dominant) is a
common disorder of keratinization
• Characterized by mild generalized scaliness clinically
19.13 Acrodermatitis enteropathica and reduction of the granular cell layer histologically.
Classification
Etiology: • Ichthyosis vulgaris (IV)
• Autosomal recessive disorder • X-linked ichthyosis (XLI)
• Genetic defect in intestinal zinc specific transporter • Lamellar ichthyosis (LI)
SLC39A4 • Non-bullous ichthyosiform erythroderma (NBIE)
Clinical features: • Epidermolytic hyperkeratosis (EHK)
• Usually manifests during the period of weaning. Etiology:
• Skin lesions - vesiculobullous, dry, scaly lesions • Ichthyosis vulgaris: Autosomal dominant. Due to
symmetrically distributed in perioral, acral and reduced or absent filagrin (responsible for formation
perianal areas of keratin filaments).
• The hair has reddish tint and alopecia of some extent • X-linked ichthyosis: Deficiency of steroid sulfatase
is characteristic. enzyme.
• Ocular manifestations - photophobia, conjunctivitis, • Lamellar ichthyosis: Autosomal recessive;
blepharitis, corneal dystrophy. abnormality of gene encoding for transglutaminase.
• Superinfection with Candida albicans is common • Non-bullous ichthyosiform erythroderma:
Diagnosis: Autosomal recessive. Several defects identified.
• Based on constellation of clinical findings and • Epidermolytic hyperkeratosis: Autosomal dominant.
detection of low plasma zinc levels Defect in keratin synthesis or degradation.
Non bullous
Main Ichthyosis X- linked Lamellar ichthyosiform Epidermolytic
features vulgaris ichthyosis ichthyosis erythroderma hyperkeratosis
Age of onset 3-12 mo Birth Birth Birth Birth
Incidence Common rare Very rare Rare Rare
Clinical Fine white scales Large dark brown Collodion baby Fine branny General erythema
features on most part of adherent scales ensheathed in shiny scales and with blistering at
the body. Large lacquer membrane marked birth followed by
mosaic scales at birth. Diffuse large erythema development of
upturned at thick brown pasted developed brownish, branny,
edge on extensor scales. Erythema is later warty, brawn liquour
surface of lower minimal plaques. Skip areas
extremities. may be present
Sites of Extensors of limb. Generalized involve- Generalized with Generalised Generalised with
predilection Major flexures are ment with no sparing accentuation on erythema and accentuation in
spared. of flexures. Palms and lower limb and scaling flexures
soles are spared. flexures
Associated Hyperlinear Corneal opacities. Ectropion, Palmar and Palmar and plantar
features palms, soles Cryptorchidism eclabium, crumpled plantar keratoderma in
Keratosis pilaris ears, palmar and keratoderma more than 60%
Atopic diathesis plantar keratoderma less frequent
329
mebooksfree.com
j Prolonged topical use of salicylate results in

intoxication (salicylism)
• Oral Retinoids: Etretinate, 0.5 mg/kg, may be used in
severe cases.
19.15 Hemangioma
• An infantile hemangioma (IH) is one of the most

common benign tumors of infancy
• Occurs in approximately 5–10% of infants.
Figure 19.11 Scaly skin lesions of Icthyosis vulgaris. • Benign vascular tumors composed of an increased
number of unique endothelial cells that line blood
vessels.
Clinical features:
• They occur more frequently in female, premature and
• Generalized fine scaling over the entire skin surface, low birth weight infants.
which tends to be worse in the winter when humidity
is low and may show improvement in the summer.
• Usually appear within the first weeks of life and grow
most rapidly during the first three to six months of life.
• Scales are commonly found in
j Extensor aspects of the limbs and trunk
• IH reaches maximum size by 3–12 months of age,
followed by involution. Involution occurs slowly over
j Over the back
many years and usually complete around five years
j Lateral aspects of upper arms
of age.
j Anterolateral thighs especially over the shins
• The scaling spares the flexures, antecubital, popliteal Types of vascular tumours
fossae and axillae • Infantile hemangioma
• The scales are large, polygonal and adherent (fish- • Congenital hemangioma
scale pattern) on the extensor surfaces of the • Angiokeratoma
extremities (Fig. 19.11). • Age of onset: usually begin after birth
• Keratosis pilaris (follicular “spines” due to plugging of • Evolution: Initial growth followed by involution (in
follicular orifices by horny debris) may be seen over infantile hemangioma)
the outer aspects of the upper arms in a few subjects. • Underlying skeletal defects: Infrequent
Differential diagnosis: Complications:
• Hypothyroid states and malnutrition • Ulceration, Bleeding
Management: • Site specific complications
• Emolients: Cases with severe scaling requires topical j Larynx - Breathing is compromised
j Eye - Amblyopia
keratolytic agents.
j Bone - Erosion
j Preparations containing urea in concentrations of
j Heart - High output heart failure
10-15% and salicylic acid in concentrations of 1-6%.
Clinical features of vascular birth marks:
Infantile hemangioma Salmon patch Port wine stain Lymphangioma

Onset After birth At birth At birth At birth
Morphology Soft, bright nodule with Telangiectatic Light pink, red macules, Cluster of thin-
pale stippling macules bosselated with age walled vesicles
(Fig. 19.12A) (Fig. 19.12B)
Site Face and neck Nape of neck, face Trunk
forehead, eyelids
Complications Interfere with function, none Sturge-weber syndrome
bleeding or ulceration associated with hamartomas;
seizures, eye deficits
Course Grows for few months; Involutes by 1 Persists throughout life persists
regression by 5 years year
330
mebooksfree.com
Figure 19.12 A, Strawberry hemangioma. B, Port wine stain.
• Large segmental hemangioma of Head and neck - • Port wine stain- cosmetic camouflage, laser ablation
PHACES syndrome with pulsed-tunable dye laser
Treatment: • Lymphangioma-surgery, carbon dioxide laser,
• Salmon patch- No treatment required radiofrequency ablation.
• Infantile hemangioma-
j Small lesions resolve spontaneously. Online supplementary materials:
j Large symptomatic lesions need treatment with Please visit MedEnact to access chapter wise MCQs and
systemic steroids in the proliferative phase. previous year pediatrics theory questions asked in various
j Propanolol therapy under supervision shows final MBBS University examinations.
dramatic result in upto 30–50% cases.
j Pulsed-tunable dye laser is used for cosmetic results
331
mebooksfree.com
Chapter | 20 |
Poisoning and envenomation
Clinical features suggesting poisoning

20.1 Poisoning • Acute onset of symptoms
• Unexplained multisystem involvement
Introduction: • Unexplained metabolic acidosis
• Approximately 85% cases of childhood poisoning • Acute renal failure
occur in ‘under 5’ age group. This is explained by • Acute liver failure
their exploratory behavior, finger-mouth activity, • Arrhythmias, in a previously normal child. Common
pica, relative hyperactivity seen during that age. In clinical clues and toxidromes are summarized in
developing countries, pesticides and plant derivative Table 20.1 & 20.2.
poisoning are commonly seen while pharmaceuticals Bedside Tests for Toxin Identification
and chemicals form the major cause of poisoning in These tests help in identifying suspected toxin before re-
the developed world. sults of other tests are available.
• Common causes of poisoning in children are Urine Tests
household products like kerosene oil, drugs,
• Urine should be examined for abnormal color and odour.
chemicals and pesticides. While majority of the Smoky dark green urine on standing is seen with phenol
poisoning are accidental, intentional (Suicidal or poisoning. Plenty of oxalate crystals are characteristic
homicidal) should be considered whenever suspicion of ethylene glycol poisoning. Ketones in urine suggest
arises. poisoning due to acetone, salicylate or isopropyl alcohol.
Approach to a child with suspected poisoning Ferric chloride test:
• A general ‘two pronged model’ approach is used • Helps in identifying suspected toxin
in the management of suspected poisoning cases
• Add 5-10 drops of freshly prepared 10 % ferric chloride
(Fig. 20.1). The left-sided prong begins with basic solution to 10 ml of boiled and acidified urine.
emergency treatment including care of airway,
• Change of color indicates specific poisons
breathing and circulation. Decontamination and j Red in salicylate poisoning
prevention of continued exposure by removing j Purple green in phenothiazine poisoning
clothes etc. Supportive therapy with treatment of j Violet in phenol poisoning
symptoms, maintenance IV fluids, treatment of fever,
dyselectrolemia, acid base disturbances and organ Blood Tests
involvement. Once diagnosis is confirmed, focused • Blood gas analysis detects anion gap and acid base
therapy involving antidote administration or removal disturbances by measuring ions and osmotically
of poisoning from system (dialysis) should be started. active agents in blood. Blood appears ‘chocolate
• The right-sided prong focuses on specific diagnosis based brown’ in patients with methemoglobinemia and
on history, examination findings, recognising toxidromes, turns pink on addition of potassium cyanide.
running diagnostic tests and toxicology analysis. In real Gastric Aspirate
life situation, both diagnosis and treatment happens • In cases of iron poisoning, addition of two drops of
simultaneously. High index of suspicion is required when 30% hydrogen peroxide and deferoxamine (0.5 ml,
dealing with infants and toddlers. 125 mg/ml) to 1 ml of gastric fluid leads to color change
332
mebooksfree.com
Poisoning and envenomation Chapter | 20 |
Other laboratory tests that help in identification of poisons

• Complete blood counts
• ECG
• Chest Xray
• Echo Heart
• Liver and Renal function tests
• Xray abdomen for iron poisoning
• Xray long bones for lead poisoning
Management
• High index of suspicion and early institution of
appropriate management forms the basis of therapy.
• Resuscitation and stabilization are the first
priority as soon as the child reaches the hospital.
Decontamination and administration of specific
antidote should be done simultaneously or as soon
Figure 20.1 Two pronged approach to a child with as feasible. During resolution phase, supportive
suspected poisoning. care and monitoring should continue until clinical
and laboratory abnormalities have resolved.
Table 20.1 Clinical clues to identify specific poisons A) Resuscitation & Supportive Therapy
Airway Maintenance & Breathing
Features Toxin ■ Difficult airway should be anticipated in caustic
and thermal upper airway injuries, neck, facial
Bradycardia Digitalis, organophosphates, beta injuries and in cases of angioedema. Oral cavity
blockers, opioids should be inspected and any food particles,
Tachycardia Atropine, salicylate, amphetamine vomitus, secretion and dentures should be
removed. Airway should be secured immediately
Fever Atropine, Organophosphorus,
in comatose children. Bag and mask ventilation is
salicylates, theophylline, quinine
associated with a higher risk of aspiration. Risk of
Miosis Organophosphates, opioids, aspiration can be reduced with left lateral position,
barbiturates Sellick’s maneuver and aspiration of gastric
Paralysis Botulism, heavy metals contents prior to ventilation. To prevent tongue
from falling back, an oropharyngeal airway tube
Jaundice Acetaminophen, carbon tetrachloride can be inserted.
Table 20.2 Common toxidromes (Constellations of specific signs and symptoms associated with poisoning)
Anticholinesterase Sedative,
Findings Adrenergic Anticholinergic (cholinergic) Opioid hypnotic
Heart rate Increased Increased Decreased Decreased Arrhythmia, QT
prolongation
Temperature Increased Increased Normal Normal Normal
Pupil Dilated Dilated Constricted Constricted Dilated
Mucosa Wet Dry Wet Normal Normal
Skin Diaphoresis Dry Diaphoresis Normal Normal
Respiratory Tachypnea Tachypnea Wheeze Hypoventilation hypoventilation
Tachypnea
↑ secretions
Neurologic Agitation Agitation Coma Sedation Convulsions
Tremors Hallucinations Fasciculations Coma
Seizures Myoclonus
Hallucinations Hyperreflexia
333
mebooksfree.com
Circulation aspiration. Airway should be secured in comatose

■ Pulse volume and blood pressure should be patients or in poor gag reflex before performing
assessed. Hypotension is a recognized feature of lavage. Lavage should be done with 10 - 20 ml/
acute poisoning, but classic features of shock like kg of normal saline until clear fluid is drained.
tachycardia and pale cold skin are rarely seen. Activated charcoal should be instilled after the
j Fluid boluses should be promptly given in cases lavage is completed.
of shock along with monitoring for fluid overload. Binding agents:
In cases of cardiogenic shock, secondary to ■ Activated charcoal, clay and cholestyramine are
cardiotoxic agents or in children with pre-existing used to reduce absorption of ingested toxins.
cardiopulmonary diseases, fluid boluses should j Activated charcoal is the ideal binding agent with a
be avoided. In fluid unresponsive shock and total adsorptive surface of 1600 to 1800 m2/g.
cardiogenic shock, inotropes are started. Central j It is used at a dose of 1-2 g/kg. It is available as a
venous pressure and urine output should be 400 mg tablet and should be crushed, made into
monitored during fluid therapy. slurry before administration. Efficacy is maximum
Convulsions if started within one hour of toxin ingestion.
■ Convulsions may occur in poisoning due to j Activated charcoal is an effective nonspecific
tricyclic antidepressant (TCA), mefenamic acid or adsorbent used in most cases of poisoning,
opioids. For convulsions, IV diazepam 0.3 mg/ regardless of interval since ingestion. However,
kg should be administered. IV diazepam can also it should be avoided in patients with corrosive
be given IM or Rectal if IV access is unavailable. ingestion, ileus, intestinal hemorrhage and patient
IV Phenytoin (20mg/kg) and IV Phenobarbitone with unprotected airway who is at risk for aspiration.
(20mg/kg) are second line drugs to be considered. Cathartics:
Phenobarbitone can cause respiratory depression. j Routine use of cathartics either alone or with
Stress Ulceration and Bleeding activated charcoal is not recommended.
■ Stress ulceration of stomach can be prevented by j Whole bowel irrigation with polyethylene glycol
administering IV proton pump inhibitor or H2- is the only procedure, which decontaminates
receptor blockers. Nasogastric tube should be in beyond the pylorus without causing emesis or
place in cases of ongoing gastric bleeding. Child fluid overload and dyselectrolytemia. It is used in
should be kept ‘Nil per oral’ during active bleeding. patients with ingestion of sustained release drugs,
B) Prevention of Further Absorption of Poison from slowly dissolving agents, ingested crack vials and
skin and mucous membranes drug packs. Whole bowel irrigation can be achieved
■ Application of water to dilute poison and reduce with administration of 500 ml/hour of polyethylene
exposure should be done. Clothes should be glycol over 4-6 hr. The procedure is safe, with rare
removed and the contaminated area should be side effects of rectal itching and vomiting.
washed with water and soap. Neutralization C) Increasing Elimination of Poison
with chemicals (using alkali for acid exposure or Manipulation of Urine pH and diuresis:
vice versa) is harmful and contraindicated. Skin j Elimination of ingested substances that are
cleaning should be done regardless of duration of excreted by kidneys can be augmented by
exposure. Oral cavity and eye should be washed increasing GFR or altering urine pH. Acidification
with plenty of water. of urine will enhance elimination of weak bases
Gastrointestinal decontamination: but rarely used clinically.
■ Most preferred procedure for decontamination is j Alkalization of urine is used in poisoning due
activated charcoal with or without whole bowel to weak acids like salicylate, phenobarbital and
irrigation. Ipecac induced emesis and cathartics herbicides.
are not recommended as gastric emptying j Sodium bicarbonate is commonly used for this
procedures. Other emetics like apomorphine, purpose and administered at a dose of 1-2 mEq/
detergent, raw egg and dry mustard powder are kg every 3-4 hr, with a target of maintaining
also not used. urine pH between 7 and 8. Sodium bicarbonate
Orogastric lavage. is also effective in reducing the toxicity of tricylic
■ The role of orogastric lavage in children is not antidepressants and quinine.
clear but can be tried in certain specific situations. Dialysis:
It is contraindicated in corrosive poisoning. j The mode of dialysis depends upon clinical
Gastric lavage should be considered only when a condition, available resources and type of ingestion.
potentially lethal toxin has been recently ingested j Peritoneal dialysis is more effective in children
in the last 1 hour. Lateral decubitus position due to larger peritoneal surface in relation to
with lowering of head end is preferred to avoid body surface area. It enhances elimination of
334
mebooksfree.com
Table 20.3 Antidotes
Poison Antidote Dose

Acetaminophen N- acetyl cysteine Loading dose-140mg; maintenance-70mg/kg q
4hrly X 17 doses
Anticholinergics Physostigmine 0.02 mg/kg slow IV
Benzodiazepines Flumazenil 0.01 mg/kg bolus or total dose of 1-3 mg
Digoxin Digoxin immune antibody fragment 10-20 vials IV bolus in emergency
Methemoglobinemia Methylene blue 1-2 mg IV/kg slow IV
Opioids Naloxone 0.4-2 mg IV
Organophosphates Atropine 0.1 mg/kg IV repeat dose titrated to effort
Salicylates Sodium bicarbonate 150 mEq+ 40 mEqKCl in 1L of 5% dextrose
Ethylene glycol Fomepizole 15 mg/kg IV stat; 10mg/kg/dose q12hrly X 4 doses
Methanol
compounds like alcohol, lithium and salicylates.

Often used as a temporizing measure before 20.2 Paracetamol poisoning
hemodialysis or hemoperfusion can be arranged.
j Hemodialysis is the preferred method for removal
of compounds like bromide, chloral hydrate,
• Most common, safest analgesic and antipyretic used
in children. A dose above 200 mg/kg in children
ethanol, methanol, ethylene glycol, lithium and
below 12 years or single dose of 7 g is lethal.
salicylates. It also rapidly corrects metabolic
Liver is the primary organ to be involved but renal
abnormalities and fluid overload. The procedure
tubular damage and hypoglycemia can also occur.
has risks of bleeding or thrombosis, hypotension
Hepatic damage with paracetamol overdose begins at
and nosocomial infection. It is technically not
>150 mg/kg due to a reactive metabolite N-acetyl-p-
feasible in infants and toddlers.
benzoquinonimine (NAPBQI) and due to glutathione
j Hemoperfusion involves pumping of blood
depletion
through activated charcoal or carbon with large
surface area leading on to effective removal of Clinical Features
substances by adsorption. Preferred method for • Four classical clinical stages of paracetamol toxicity
elimination in drug overdoses (Eg: carbamazepine, are described in literature:
phenobarbital, phenytoin and theophylline).
Alcohol, lithium, many heavy metal poisons Hours since
are not adsorbed by activated charcoal. Stage ingestion Characteristics
Thrombocytopenia, leukopenia and hypocalcemia Stage 1 12-24 hrs • Anorexia, nausea, vomiting,
are commonly associated complications. cold sweats are present
j Exchange transfusion can be considered in • Liver function test (LFT)
neonates and infants. It removes poisons affecting and prothrombin time (PT)
the red blood cells (as in methemoglobinemia are normal
or arsine-induced hemolysis). The elimination Stage 2 24-48 hrs • Resolution of Stage-1
of heavy metals is enhanced by chelation and symptoms
removal of carbon monoxide can be increased by • Appearance of upper
hyperbaric oxygen therapy abdominal pain,
D) Specific therapy hepatomegaly & Jaundice.
Administration of Antidotes • Biochemical evidence of
Antidotes neutralize the effects of poisons by hepatorenal injury
antagonizing their physiologic effects, thereby • Elevated bilirubin and
significantly reducing the morbidity and mortality. prothrombin time (PT)
Their safe use requires correct identification of specific • Elevation of hepatic
poisoning or syndrome. Table 20.3 summarizes transaminases to above
common antidotes for poisons used clinically. 1000IU/L
335
mebooksfree.com
j If paracetamol is ingested along with

Hours since
anticholinergics or opioids
Stage ingestion Characteristics
Management
Stage 3 48-96 hrs • Re-appearance of Anorexia, Antidote:
nausea, vomiting and pallor • N- acetyl cysteine (NAC) is the specific antidote and
• Phase of Peak is used orally within 16 hrs after ingestion. It is not
hepatotoxicity – Liver
effective if given after 24 hours of ingestion. Drug is
biopsy shows centrilobular
often mixed with fruit juice and given orally
necrosis
• Acute renal failure. • Contraindications to NAC
j Coma, vomiting, hepatic failure/encephalopathy
Stage 4 4-14 days • Phase of Recovery – Return j Pre-treatment with activated charcoal
of consciousness and
improvement in hepatic Oral regimen • Loading dose 140 mg/kg NAC
function tests. Histological orally followed by maintenance
recovery takes 3 months dose-70 mg/kg q4 hr for 17
additional doses.
IV regimen • Within 8–10 hours of ingestion
• With lethal doses, Death occurs within 16 hrs after • Loading dose of 150 mg/kg
ingestion. infused over 1 hour, followed
Investigations: by first maintenance dose of 50
• Serum paracetamol levels should be measured after mg/kg over 4 hours followed by
4 hours following ingestion. second maintenance dose of 100
mg/kg over 16 hours
• Liver function tests (Serum Bilirubin, PT, SGPT,
SGOT) should be serially monitored
• Diagnosis of hepatotoxicity is done by Rumack-
Matthew nomogram (Fig. 20.2) Supportive therapy:
• Rumack-Matthew nomogram is not useful in the • Correction of hypoglycaemia
following situations • Maintenance of hydration
j Poisoning with sustained release formulation • Electrolyte balance
j Chronic poisoning • Treatment of coagulopathy
• Hemodialysis for acute renal failure
• Management of fulminant hepatic failure
Prognosis
• Prognosis in general is good for cases receiving
treatment. Even with significant hepatotoxicity,
complete recovery occurs in most cases.
• Poor Prognostic Factors:
j Blood pH < 7.3
j Prothrombin time >100 sec
j Grade 3 or more hepatic encephalopathy
j Elevated serum bilirubin> 4 mg/dl
j SGOT > 1000 IU/L
j Ratio of Factor 8: Factor 5 > 30
20.3 Kerosene poisoning
• Aliphatic hydrocarbons including kerosene, turpentine,

lubricating oils and tar, have the greatest risk of
aspiration and pulmonary symptoms. Aromatic
compounds like benzene are Neuro and hepato-toxic
• Type of toxicity depends on-
j Volatility
Figure 20.2 Rumack-Matthew nomogram. j Viscosity
Source: TIETZ Fundamentals of CLINICAL CHEMISTRY, 2008 j Surface tension
336
mebooksfree.com
• Lower viscosity, higher risk of aspiration eg, mineral ongoing dermal absorption. Gastric emptying and
oil, kerosene, furniture polish induced vomiting are contraindicated due to the risk
• Substances with high volatility and low viscosity of aspiration. Commonly used household antidotes
(naphtha in lacquer diluent) - Act as toxins through such as milk and oil should be avoided.
inhalation causing neurological depression • Oxygen and respiratory support are mainstay therapy
• Kerosene poisoning is the most common accidental in symptomatic children. Oxygen saturation should
poisoning seen in children from tropical countries be continuously monitored during acute phase. Beta
where Kerosene is a major fuel used for cooking. agonists nebulisation might offer symptomatic relief
Commonly seen in toddlers and pre-school children. in patients with predominant wheezing.
Storing kerosene in disposable water or cool drink • Steroids have no role in treatment. Though
plastic bottle is a risk factor. prophylactic antibiotics are commonly prescribed in
practice, the benefits are uncertain.
Pathogenesis
• Children who are asymptomatic for 6 hours can be
• Kerosene is an open chain, aliphatic, low viscosity discharged from hospital. Morbidity and Mortality is
hydrocarbon. Due to its chemical property, it
high among malnourished children.
carries a significant risk of aspiration and chemical
pneumonitis.
• Kerosene is not absorbed from gastrointestinal tract.
Hypoxia secondary to aspiration pneumonia causes 20.4 Lead poisoning (Plumbism)
neurological symptoms. Neurological complications
are unlikely in the absence of lung involvement
• Fatal dose- 30 ml • It usually occurs in children suffering from pica
• Common mode of poisoning includes ingestion of
Routes of exposure: lead paint flakes, old paint chips and inhalation of
• Accidental ingestion among children fumes from batteries or from applying kajal or surma
• Transdermal absorption via skin of neonates containing black oxide of lead in eyes
• IV kerosene injections among IV drug abusers. • Lead is a toxic metal that has 4 isotopes, low melting
Clinical features: point and ability to form stable compounds.
• Immediate symptoms include violent coughing, • Blood lead level (BLL) is gold standard for determining
flushing of the face and vomiting following ingestion. health effects. Normal BLL is below 5 µg /dL (reference
Examination invariably reveals the characteristic value based on the 97.5th percentile of the population)
kerosene odour from mouth and vomitus. Symptoms Risk factors:
usually begin within 6 hours of ingestion. Late
• Use of tetraethyl lead as a Petroleum additive
manifestations are rare.
• Usage of lead containing solder to seal cans of food
• Respiratory findings include cough, tachypnea, and beverages
retractions, wheeze and crepitations.
• Lead used in household paint.
• Older children often complain of headache,
abdominal pain abdominal distension, dry Toxic compounds
throat and difficulty in swallowing. Fever is very of lead Uses
common. Pnemonitis in seen in one fourth of the
cases. Neurological manifestations in the form of Lead acetate Astringent and local
restlessness, convulsion and coma can occur in severe sedative for sprains
cases. Lead tetraoxide Used as sindoor
Radiological changes: Tetraethyl lead Antiknock for petrol
• Xray changes are seen after 6 hours of ingestion. Lead sulfide Applied on eye
• In asymptomatic cases, Chest xray is ordered after Lead carbonate Manufacture of paints
6 hours and immediately in symptomatic cases.
• Common findings include basilar infiltrates and
emphysematous changes. Rarely pleural effusion and Sources of lead:
pneumatoceles can be seen.
• Paint chips
Management: • Home remedies (antiperspirants, deodarants)
• All suspected cases should be hospitalized. Preserving • Stored battery casings
airway is of utmost importance in unconscious • Lead based gasoline
patients. Patients should be put on left lateral • Cosmetics (kajal, kohl, surma)
position to avoid aspiration. Decontamination of the • Lead plumbing (water)
skin and removal of contaminated dressings prevent • Lead coated cooking utensils
337
mebooksfree.com
Metabolism: • In Chronic poisoning, lead lines can be seen in

• The non-nutritive hand to mouth activity of young skeletal radiographs
children is the most common pathway for lead to Treatment:
enter the body. Though mostly ingested as solids or
• In acute, massive ingestion of lead, vomiting is
liquids, organic lead compounds like tetraethyl lead, induced immediately followed by administration of a
can also be absorbed through skin. saline cathartic.
• Lead is absorbed well when ingested with empty • Specific treatment includes a combination of
stomach. Calcium and iron may decrease lead dimercaprol (BAL), 4 mg/kg/dose every 4 hours
absorption by competing for binding sites. Iron intramuscularly, and calcium EDTA, 12.5 mg/kg/
deficiency can result in enhanced lead toxicity. dose every 4 hours intramuscularly or intravenously.
• After absorption, 97% of lead circulates bound to These drugs are discontinued after 2 days and oral
RBC. Lead preferentially accumulates in bones. penicillamine, 25 mg/kg/ day is given for 5 days.
Plasma portion may enter cell and enhance Chelating therapy can be stopped when lead levels are
toxicity. below 60 mcg/dL. BAL is avoided in the presence of
• Lead binds to enzymes with sulfydryl groups hepatic failure.
and interferes with mitochondrial oxidative
phosphorylation. It also hinders the function of Prevention
ATPase, calcium dependent messengers and enhances • Identification and elimination of environmental
apoptotic cell death. sources of lead exposure (attractive lead toys, pencils,
paints)
• In heme pathway, enzyme ferrochelatase,
enables protoporphyrin to chelate iron, forming • Behavioural modification to reduce non-nutritive
heme. Heme is essential for multiple metabolic hand to mouth activity
pathways. RBC protoporphyrin levels higher than • Dietary counselling to ensure sufficient intake of the
35 microgram/dL are abnormal and are consistent essential elements calcium and iron.
with lead poisoning, iron deficiency and recent
inflammatory disease.
Clinical effects: 20.5 Iron poisoning
• Polymorphism of gene coding for enzyme delta-ALA
dehydratase determines the toxicity levels and effects.
• Accidental ingestion of tablets by a toddler is a
BLL higher than 100 µg/dL in children leads to lead common problem in developing countries. Iron is
encephalopathy. BLL more than 300 µg /dL may easily available in the household as most mothers are
result in coma. anemic and receiving iron therapy.
• GIT symptoms- Anorexia, abdominal pain, vomiting, • Symptoms of toxicity appear with doses of 10
constipation (BLL >20 µg /dL) – 20 mg/kg. Lethal dose of elemental iron is
• CNS symptoms- worsening cerebral edema, approximately > 60 mg/kilogram.
increased ICT, headache, change in mentation,
lethargy, papilledema, seizures, coma Pathogenesis
(BLL > 70 µg /dL), peripheral neuropathy, wrist • Direct corrosive effect
and foot drop. • Electron sink mechanism
• Others- renal tubular dysfunction, fanconi syndrome • Free radical damage
(>100 µg /dL), haemolytic anemia. • Dose dependent coagulation dysfunction
Clinical Features
Chronic lead poisoning in older children-
• Clinical features of iron poisoning often evolves
• GIT: colic, constipation through five well described clinical stages.
• Renal: Interstitial nephritis, hypertension • The earliest manifestations include vomiting and
• CNS: Lead palsy, lead encephalopathy, optic atrophy, abdominal discomfort due to irritation of the
retinal stippling, and peripheral neuritis. gastric mucosa. Erosion of gastric mucosa may cause
• Hematological: Facial pallor, anemia, basophilic upper GI bleeding resulting in hematemesis and
stippling in blood smear, burtonian lines in gums malena.
• Others: Infertility, osteopathy, and arteriolar • Shock, CNS depression and hepatic or renal failure
degeneration, liver damage, alopecia may occur within few hours or after a day or two
Diagnosis: following a brief period of recovery.
• Porphyrinuria due to coproporphyrin 3 • Gastric scarring leading on to pyloric stenosis or
• Blood lead level >70-100 microgram/dl. intestinal obstruction can occur as late sequelae.
• Protoporphyrin >35 microgram/dl • Iron predisposes to infection with Yersinia
• Urine lead level >0.15-0.3 mg/L enterocolitica and Listeria monocytogenes
338
mebooksfree.com
Poisonous snakes
Five Duration
stages from exposure Features • Elapids → Cobra, king cobra, krait, branded kraits,
corals
Stage I Upto 6 hours GIT- Local necrosis,
hemorrhage, acidosis, • Vipers
j Pit vipers → Bamboo snake
drowsiness
j Pitless vipers → Russel’s viper & Saw scaled viper
Stage II 6 – 12 hours Apparent recovery: Iron
accumulation continues • Sea snakes
in mitochondria
Stage III 12 – 24 hours Circulatory failure: • Two types of bites- Business bites and defensive bites
Shock, coagulopathy, • Poisonous snake bite is not necessarily the same as
acute tubular necrosis, snake bite poisoning
pulmonary hemorrhage • Venom of these snakes contains neurotoxins,
Stage IV 2 – 3 days Hepatic necrosis: cardiotoxins, hemotoxin or cytotoxins
Increased bilirubin, • Hemotoxic: Russel’s and Saw scaled vipers
SGPT, SGOT, PT • Neurotoxic: Cobra and krait
Stage V 2 – 6 weeks Gastric scarring: Gastric • Both Hemotoxic and Neurotoxic: Russel’s viper
outlet obstruction, Clinical features
intestinal obstruction • Pain, tenderness, swelling, bleeding and blister
formation at the bite site.
• Initial symptoms- Nausea, vomiting, abdominal pain
Diagnosis and headache
• Iron tablets are radiopaque can be visualized in plain • Tissue necrosis ( Viper and cobra)
Xrays. • Neurotoxicity (Sea snake, Cobra, Mamba, Coral snake)
• High anion gap metabolic acidosis j Ptosis
• Serum Iron levels j Diplopia
j Less than 50 mcg/dL: No toxicity j Bulbar palsy progressing to dysarthria
j Greater than 50 mcg/dL: Toxicity manifests j Generalized weakness
j Greater than 350 mcg/dL: Toxicity evident, May be • Coagulopathy (Viper, Australian elapids)
lethal j Bleeding from bite site
Treatment j Gum bleeding
Epistaxis
• Initial management includes gastric lavage along with j
administration of sodium bicarbonate. Vomiting j Intracranial bleeding

should be not induced due to the risk of aspiration. • Rhabdomyolysis (Rusell viper, Sea snake, some
Activated charcoal is ineffective as it does not bind iron. Australian elapids)-
Muscle pain and tenderness
• The antidote of choice is deferoxamine, 90 mg/ j
kg/day in 4 to 6 divided doses intravenously or j Dark urine

intramuscularly. Deferoxamine, 1 g chelates 90 mg j Acute tubular necrosis
of elemental iron. Therapy should be continued • Hypotension or shock, myocardial toxicity,
till urine color is normal or serum iron <300 mcg/ hypovolemia
dL. Other antidote used is calcium EDTA, 12.5 mg/ Investigations:
kg intramuscularly. Rarely, dialysis or exchange • CBC ( RBC, WBC, Platelet count, Haematocrit)
transfusion might be necessary • Urinalysis
• A careful monitoring of fluid, electrolyte and acidbase • Electrolytes, BUN, Creat, ECG.
balance along with prompt intervention if required is • Creatinine kinase
essential. • 20 minutes Whole Blood Clotting Time
General Approach:
• The steps in management are :
First aid treatment
20.6 Snake bite
j
j Transport to hospital
j Rapid clinical assessment & resuscitation
• Snake bites cause 125000 deaths annually worldwide. j Detailed clinical assessment & species diagnosis
Young adults from rural areas are commonly j Investigations/laboratory test
involved. j Antivenin treatment
• About 400 of 3000 snake species are poisonous j Supportive treatment
339
mebooksfree.com
j Rehabilitation • Direct cardiotoxicity

j Treatment of chronic complications • Hypovolemic or haemorrhagic features
The first aid recommended is based around the mnemonic: • Respiratory failure – neurotoxic envenomation
• Sudden deterioration /rapid development release of
• Do it RIGHT (Mnemonic) tourniquet
• R- Reassuring the patient • Cardiac arrest – hyperkalemia – rhabdomyolysis
• Immobilize the limb in a functional position
Early clues of severe envenomation:
below the level of heart
• G,H- Get to the hospital immediately • Snake identified as a very dangerous one
• T- Tell the doctor of any symptoms during transit • Rapid spread of local swelling from site of bite.
• Early tender enlargement of lymph nodes
• Wound is cleansed thoroughly without using alcohol • Early systemic symptoms
• Pressure immbolization to decrease venous • Early spontaneous bleeding
outflow may delay systemic absorption of venom
• Passage of dark urine
that contains primarily neurotoxins but is not
recommended for venoms with cytotoxins since they
may worsen local necrosis • Incision and suction by mouth or using mechanical
devices are ineffective and should be avoided.
Rapid assessment:
• Identification of snakes (Fig. 20.3 A–D) requires
Scenarios requiring urgent resuscitation knowledge of local snake fauna, snake morphology,
• Profound hypotension & shock venom kit testing and clinical syndrome.
Figure 20.3 (A) Russel’s Viper (B) Saw scaled Viper (C) Krait (D) Cobra (Pic Courtesy: Mr. Gladwin John, Tirunelveli)
340
mebooksfree.com
• During transportation to the hospital, to prevent Principles of ASV therapy:

absorption of toxin, a tourniquet can be applied • The physiological basis of ASV dosing is to neutralize
proximal to the bite about 5 cm above the upper limit average dose of venom injected
of swelling which allows one finger beneath. It should • Eg: Russels viper average 63 mg venom /bite. 1 vial
be left till anti-snake venom (ASV) is administered. of ASV neutralizes 6 mg of RV venom. So initial
• The bitten part should be immobilized and placed in dose of 8 – 10 vials of ASV is absolutely necessary to
a dependent position. neutralize average venom injected per bite.
Hospital Management: • Total range of venom injected by all species is
5 – 147 mg which translates into maximum of 25 vials
• Fang bites are often obvious in cobra, viper bites
due to local tissue necrosis but can be missed in • In India, polyvalent ASV contains antibodies against
Australian elapids venom of all four common species, Russell’s viper,
common cobra, common Krait and saw-scaled viper.
• Due to infrequent envenomation by most snakes,
patients require just observation No species specific antivenin is currently available
• Clinical and laboratory assessment and management • Skin test by intradermal injection of 0.1 ml of 1:100
should focus on supportive care for specific syndromes saline dilution of AVS. Hypersensitivity is indicated
by appearance of a wheal of > 10 mm in 10 to 30
• Continuously monitor vital signs, fluid status, central
venous pressure for patients with shock. Whole minutes
blood clotting time (WBCT) >20 minutes is an useful • Conjunctival test by instilling one drop of 1:10
screening test for coagulation dysfunction seen with dilution in saline in lower conjunctival sac.
hemotoxic snake bites. It is repeated every 6 hourly to Hypersensitivity is indicated by development of
monitor progression and response to ASV. conjunctivitis and tears in 10 to 30 minutes
• Administration of adequate amount of antivenom is • ASV given best within 4 hrs but can be given upto 2 -
the only specific management for envenomation. 3 wks in hemostatic abnormalities
• The current accepted management algorithm is • Antivenin should be given intravenously over 1 hour.
depicted in Fig. 20.4 Patient should be observed for at least one hour – to
detect and treat early reaction. Local administration
of antivenin not recommended. Epinephrine
Systemic envenomation Local envenomation
should always be kept ready before antivenin is
• Hemostatic • Local swelling involving administered.
abnormalities more than half of the bit-
• Neurotoxicity ten limb Observation of the response:
• Cardiotoxicity • Swelling after bite on the • General condition of patient improves. Spontaneous
• Acute renal failure digit systemic bleeding stops in 15-30 minutes.
• Dark brown urine • Rapid extension of swelling Coagulation dysfunction is corrected in 3-9 hours.
• Lab evidence of • Development of enlarged
In patients with shock, BP improves within 30 - 60
envenomation lymph node
minutes and sinus bradycardia resolves. In neurotoxic
Figure 20.4 Snake bite Management – Algorithm.
341
mebooksfree.com
envenomation, improvement is seen in 30 minutes. • Severe excruciating pain radiating along

Active hemolysis and rhabdomyolysis starts subsides corresponding dermatomes and life threatening
in few hours systemic effects may be noted
Dose • Scorpion venom is more potent than snake venom or
• Snakes inject the same dose of venom into children cyanide
& adults. So children must be given exactly the same
dose of antivenin as adults. Pathophysiology (Fig. 20.5):
• Scorpion venom is a complex mixture of
Recurrence mucopolysaccharides, hyaluronidase, phospholipase,
• Hemotoxic viper bites may require recurrent doses acetylcholinesterase, serotonin, histamine, protease
of ASV. Signs of systemic envenomation may inhibitors, histamine releasers and neurotoxins.
recur within 24 - 48 hrs. Recurrence of neurotoxic
• They stimulate alpha receptors causing hypertension,
envenomation is also described in literature. tachycardia, myocardial dysfunction, pulmonary edema
Criteria of repeating initial dose and cool extremities. Can also lead to DIC, intracerebral
• Persistence or recurrence of blood incoagulability haemorrhage, necrosis of liver and cytokine storm.
after 6 hrs / brisk bleeding after 1-2 hrs
• Neurotoxin acts by inactivating Na channels leading
• Deteriorating neurotoxic or cardiovascular signs after on to autonomic dysfunction
1 - 2 hrs
• Hemodynamic changes are secondary to transient
Neurotoxic envenomation cholinergic effects, and secondary prolonged adrenergic
• Mechanical ventilation in patients with bulbar and effects and or sever inflammatory response syndrome
respiratory paralysis • Serotonin is the major factor responsible for pain in
• Neostigmine (0.05 mg/kg ) ½ hrly for five doses & the sting site.
then every 2-6 hrly
Clinical features:
General Supportive measures
• The severity and spectrum of manifestations depends
• Broad spectrum antibiotics on the type of species, venom dose/weight of victim
• Prophylaxis against tetanus and gas gangrene. and site of bite.
• FFP, platelets and Packed cell transfusion • Pain is the earliest symptom that starts within seconds
• Restriction of fluids, electrolytes and dialysis in Acute to minutes after the sting. Small children present with
renal injury
irritability and incessant cry. There is minimal or no skin
• Surgical debridement in case of gangrene. reaction at sting site. Pain severity progresses during first
5 hours and usually subsides within 24-48 hours. Older
children may also complain of paresthesia near the sting
site, especially during recovery. Severe shock like pain
20.7 Scorpion sting felt on tapping over the sting site may be present (Tap
test). Patients with severe local pain do not have further
• Scorpion sting in children is an acute life-threatening, progression of symptoms.
rural medical emergency. Highly prevalent in tropical • An autonomic storm is a common presentation
regions, dry rural areas in south and central India. characterized by transient parasympathetic activity
• Envenomation with 30 of 1500 known scorpion followed by prolonged sympathetic stimulation.
species (Buthidae or Scorpionidae family) can result • Features of Parasympathetic stimulation
in neurotoxicity, cardiovascular toxicity or respiratory j Vomiting
dysfunction. j Profuse sweating
• Clinically important species in India j Hypersalivation
j Mesobuthus tumulus (Indian red scorpion) j Bradycardia
j Palamneus swammerdami (Indian black rock j Ventricular premature contraction
scorpion) j Priaprism
• Dominant clinical effects following the sting vary j Hypotension
from species to species. • Features of Sympathetic stimulation
• Predisposing factors j Peripheral circulatory failure - Cold extremities
j Warm dry regions j Hypertension
j Night time j Tachycardia
j Summer months j Myocardial dysfunction
• Scorpion stings are primarily due to accidental contact j Pulmonary edema
with scorpion. Scorpions use their stings only when j Shock
roughly handled. Scorpion does not always inject • Many patients show hypertension and/or left
venom when it stings since it can control its ejaculation ventricular dysfunction at presentation. The onset
342
mebooksfree.com
Figure 20.5 Pathophysiology of Scorpion sting.
and progression of symptoms is rapid with maximum Investigations

severity within 5 hrs. • Chest Xray – May show features of pulmonary
• Children show earlier onset of symptoms edema
(15 - 30 min in infants) and are more likely to require • ECG to look for evidence of myocarditis –
intensive supportive care. j Peaked T waves in V2-6
Clinical Grading of Scorpion sting severity j ST segment elevation in leads I, aVL
j Increased QR duration (ventricular activation
Grades Features time)
LVH by voltage criteria.
Grade -1 Local pain and paresthesia at the sting
j
site without inflammation j Low voltage complexes indicate poor prognosis

• Echocardiography - To look for
Grade – 2 Local symptoms, remote pain and j Left ventricular systolic dysfunction.
paresthesias
j Left ventricular dilatation with regional wall
• Radiating proximally up the affected
motion abnormalities are also seen
limb or generalised
Grade – 3 Cranial nerve dysfunction Management:
• Blurred vision • The management of scorpion stings involves relief
• Involuntary conjugate of pain (paracetamol or ibuprofen), wound cleaning
• Slow and roving eye movements and tetanus prophylaxis.
• Slurred speech • Severe cases with restlessness, fasciculations,
• Tongue fasciculations hypersalivation, cranial nerve dysfunction and roving
• Hypersalivation(Or)
eye movements require monitoring for respiratory
Somatic neuromuscular dysfunction
distress, hyperthermia, rhabdomyolysis and multi
in an alert individual
organ failure.
• Restlessness
• Fasciculation • Fluid balance should be maintained
• Alternating ophisthotonus and to correct losses due to vomiting, sweating
emprosthotonus and salivation.
Grade - 4 Presence of both cranial nerve
• Oral secretions should be suctioned frequently and
the need for intubation and mechanical ventilation
dysfunction and somatic skeletal
anticipated in patients who cannot maintain airway
neuromuscular dysfunction
or develop pulmonary edema.
343
mebooksfree.com
• Midazolam infusion helps to provide sedation and nitroprusside infusion or use of an ACE
relief from muscle spasticity. inhibitor.
• IV fentanyl is preferred to morphine for pain relief, j In pulmonary edema, inotropes (dobutamine:
since it does not cause histamine release 5-15 mg/kg/min) with vasodilatation through
• Prazosin – Indicated in all cases with autonomic sodium nitroprusside (0.3-5 mg/kg/min) or
storm and peripheral circulatory failure. nitroglycerine (5 mg/min) infusion is preferred.
j Competitive post-synaptic alpha1, adreno-receptor • Scorpion antivenom
antagonist j Reverses the excitatory effects of the venom
j It reduces preload, afterload and blood pressure and neutralizes circulating unbound venom to
without causing tachycardia and increase in minimize parasympathetic stimulation
myocardial oxygen demand j Its use reduces the duration of symptoms and the
j Useful in management of vasoconstriction and need for benzodiazepines
hypertension associated with alpha receptor • Scorpion-specific F (ab) equine antivenom should
stimulation be administered as early as possible to patient with
j Recommended dose is 30 microgram/kg/dose. grade 3 or 4 neurotoxicity.
Same dose is repeated every 3 – 6 hours till • Patient can be discharged after observation for 6 hrs if
extremities are warm. there is no progression of symptoms
j Avoided in cases of hypotension and
dehydration. Online supplementary materials:
• Pulmonary edema Please visit MedEnact to access chapter wise MCQs and
j Patients with left ventricular dysfunction due previous year pediatrics theory questions asked in various
to hypertension may benefit from sodium final MBBS University examinations
344
mebooksfree.com
Chapter | 21 |
Social pediatrics
concentration of glucose and NaCl. Low osmolarity

21.1 Diarrhoea control programme achieved by reducing Na+ concentration of ORS
solution to 75 mOsmol. Improved efficacy than
Background and current scenario standard WHO ORS.
• Implemented in 1980 Treatment of diarrhea
• 1985-86 • There are three plans for the management of
j Inception of oral rehydration therapy diarrhoea:
program j PLAN A – mainly home management
j Strengthening of case management of j PLAN B – managing with oral rehydration salts
diarrhea (ORS)
j Improving maternal knowledge related to use j PLAN C – Hospital care with IV fluids
home available fluids
• 1992-93 – integrated along with Child Survival and
Safe Motherhood programme (CSSM) Plan A
• Currently this programme is under the umbrella of • In cases with no dehydration ask the child to drink
NRHM more fluids than usual, to prevent dehydration
Components • Milk rice diet in case of persistent diarrhea
1. Short Term- Appropriate clinical management • Look for dangerous signs like poor feeding,
2. Long Term-
persistent vomiting, altered consciousness etc.
a. Better Maternal Child Health care practices Plan B
b. Preventive strategies • In case of SOME dehydration.
c. Prevent diarrhea epidemics • Amount of ORS needed for rehydration- Weight x
Appropriate clinical management 75 ml given in first 4 hours
Oral Rehydration Therapy – • When rehydration is complete, maintenance
therapy should be started.
1. Safe and successful in all acute diarrhea due to any • Patients with mild diarrhoea usually can then be
aetiology treated at home using 100 mL of ORS/kg/24 hr
2. Aim: To prevent dehydration and to prevent mortality until the diarrhoea stops
3. Basis: Glucose enhances salt and water absorption
Plan C
from intestine and corrects electrolyte and water
deficit. • Preferred treatment in case of severe dehydration is
rapid intravenous rehydration. Referral to tertiary
4. Low osmolarity ORS: Reducing the osmolarity will
care hospital
avoid adverse effects due to hyper tonicity by reducing
345
mebooksfree.com
Preferred solutions • Classified as AURI (Upper respiratory tract) & ALRI

• Ringer’s Lactate Solution is mostly preferred. (Lower respiratory tract)
• Benefits of RL: Potassium concentration is low. • Constitutes 22-66% of outpatients & 12-45% of
• Ringer’s Lactate Solution with 5% dextrose is inpatients
preferred over plain RL as it prevents • In India: 10-50 children die per 10,000 episodes
hypoglycemia. of ARI
Give 100 ml/kg Ringer’s Lactate Solution divided as ARI control programme
follows:
• Govt. of India started – 1990
Followed by • 1992 – CSSM
Age Group Initially 30 ml/kg 70 ml/kg • 1997 – RCH
• Now it is Included in IMCI
Infants First 1 hour Next 5 hours
Crux of the program is to diagnose and treat chil
Older First 30 minutes Next 2 ½ hours dren with symptoms and signs of ARI at the community
level by training the field workers & early referral if ne
• Reassess every 1-2 hours for improvement of eded.
dehydration. If no improvement give rapidly. WHO protocol comprises 3 steps:
• Normal saline may be used if Ringer’s Lactate is • Case finding & Assessment
unavailable. • Case Classification
Better MCH care
• Institution of appropriate therapy
• Maternal nutrition Step 1: Case finding & Assessment
j Prenatal –low birth weight • Cough & difficult breathing in children < 5 years
j Postnatal – quality of breast milk age
• Child nutrition • Fever is not an efficient criteria
j Promotion of breast feeding
Step 2: Case Classification
j Appropriate weaning practices
j Supplementary feeding • Children are divided into 2 groups:
j Infants < 2months &
j Vitamin A supplementation
j Older children 2 – 59 months
Preventive strategies • Specific signs to be looked: In younger children,
1. Sanitation signs like feeding difficulty, lethargy, hypothermia,
2. Health education convulsions
3. Immunization measles
In infants < 2 months
Prevent diarrhea epidemics
• Epidemiological surveillance system • Pneumonia is diagnosed if RR 60/min with other
clinical signs
• PHC
j Delivery of package of curative and preventive • All cases should be hospitalized
services at community level • All cases should receive IV medications
j Activities in fields of water supply, communicable • Minimum duration of antibiotic therapy -
10 days
disease control
j Other and child health, nutrition and child • Combination of Ampicillin & Gentamicin is
preferred
health
Classification of ARI (as per WHO’s 2014 update)
Child < 2 months
• Very severe disease
21.2 Acute respiratory infection • Severe pneumonia
(ARI) control programme • No pneumonia
Child 2 months to 5 years
Introduction • Very severe disease
• Acute respiratory infection includes group of • Severe pneumonia
infections that causes inflammation of the respiratory • Pneumonia
tract from nose to alveoli. • No pneumonia (cold & cough)
346
mebooksfree.com
Social pediatrics Chapter | 21 |
Management of child less than 2 months

Symptoms/Signs • Poor feeding • Chest indrawing • No chest indrawing
• Seizures • Fast breathing • No fast breathing
• Abnormal sleep
• Stridor when calm
• Wheeze on auscultation
• Fever/low body temp.
Classify as Very severe disease Severe pneumonia No pneumonia
Treatment • Urgent referral • Urgent referral • Home care
• Maintain warmth • Keep the child warm • Counselling on danger
• Start first dose of antibiotic • Start first dose of antibiotic signs
Definition of Fast breathing /Tachypnea

• In infants < 2months: Respiratory rate of > 60/minute
• In infants 2 months – 1 year: Respiratory rate of > 50/minute
• In children 1 year – 5 years: Respiratory rate of > 40/minute
Comparison of previous and revised classification and treatment of childhood pneumonia at health facility.
a
Not able to drink, persistent vomiting, convulsions, lethargic or unconscious, stridor in a calm child or severe malnutrition.
Source: “Revised WHO classification and treatment of childhood pneumonia at health facilities- 2014.
Management of child between 2-59 months

Symptoms/Signs • Poor drinking • Fast breathing and / • No fast breathing
• Vomiting or • No chest indrawing
• Seizures • Chest indrawing
• Lethargic or unconscious
• Stridor when calm
• Associated severe malnutrition
Classify as Severe pneumonia or Very severe disease Pneumonia No pneumonia
Treatment • Urgent referral • Advice for home care • Assess and treat ear
• Start first dose of antibiotic • Give antibiotic problem/ Sore throat
• Management of fever& wheeze, if • Treat fever & wheeze • Treat fever & wheeze
present • Explain danger signs
Step 3: Institution of appropriate therapy - Antibiotics Prevention of ARI

Dosage of antimicrobials: • Keep young infant warm & away from draught
• Cotrimoxazole: 6-10 mg/kg per day • Exclusive breast feeding up to 6 months
• Chloramphenicol: 25 mg/kg every 6-8 hours • Better MCH services including Immunization
• Amoxicillin: 20-30 mg/kg/day in three divided doses • Vitamin A prophylaxis
347
mebooksfree.com
• Control air pollution j Obstetric emergencies should be promptly referred

• Personnel hygiene (feeding, weaning) to ‘First Referral Units’
• Socio economic development j Three post natal visits following delivery
j Minimum of 3 years birth spacing is encouraged
• For children
21.3 Reproductive and child health j Essential newborn care like maintaining warmth,
programme weight monitoring and promoting breastfeeding
j Specialized care for preterm and low birth weight
babies
Background
Neonates with complications are referred to
• The first phase of the program was formally launched
j
nearest health center.

on 15 October 1997. The second phase launched
j Exclusive breast-feeding and Routine
from 1 April, 2005.
immunization as per national immunization
Objectives
schedule is encouraged
• To reduce total fertility rate, infant mortality rate and j Vitamin A Prophylaxis
maternal mortality rate.
Oral rehydration in children with Diarrhea
• Population stabilisation
j
j Respiratory infection managed as per ARI control

Components program. Antibiotics and referral for sick cases
1. Family planning j Deworming, Iron supplementation and treatment
2. Child Survival and Safe Motherhood of Anemia
3. Prevention/Management Of RTI/STD/AIDS
• For Eligible Couples
4. Adolescent Health Care and Family Life Education j Promoting contraceptive use among eligible
Highlights of the program couples. Couples are educated and assisted to
• All programs related to fertility regulation, maternal choose their method of choice. Common methods
and child health and reproductive health are integrated. include condoms, oral pills, IUCDs, male and
• Client oriented, demand driven services through female sterilization
decentralized participatory process and target free j Facility to perform medical termination of
approach pregnancy should be available for mothers
• Up-gradation of facilities : Creation of First referral needing abortion
units (FRU) j Treatment of sexually transmitted diseases
• Provision of specialist services for STD and RTI j Creating awareness and implementation of
• Provision of outreach services for vulnerable groups adolescent’s health activities.
Categories RCH Program: Phase II
• Based on crude birth rate and female literacy rate • RCH Phase II began from 1 April 2005.
j Category A: 58 districts • The components are:
j Category B: 184 districts j Essential obstetrical care
j Category C: 265 districts j Emergency obstetrical care
Service Package: For mothers j Strengthening referral system
• Essential obstetric care j Strengthening project management
j Early registration j Strengthening infrastructure
j Minimum 4 Antenatal care visits j Capacity building
j Safe delivery j Improving referral system
j 3 postnatal care visits j Strengthening MIS
j Referral j Innovative schemes
• Emergency obstetric care
j Strengthen FRUs
j Supply of kits and skilled manpower 21.4 IMNCI (integrated
j TBA (Traditional Birth Attendants) Dai training management of neonatal
Local NGOs involved
and childhood illness)
j
j 24-hr Delivery services at PHCs/CHCs

j Promote institutional deliveries and additional
honorarium to staff Background
j Safe deliveries • An integrated approach to manage sick children and
j Deliveries conducted by trained healthcare to achieve better outcomes.
professionals under safe and hygienic atmosphere • Preventive, promotive and curative aspects of disease
j Institutional deliveries for High risk pregnancies management with participation of mother
348
mebooksfree.com
• Evolved from IMCI • Advise mother the steps to keep the young infant
• Five major childhood illnesses are included-Measles, warm on the way to the hospital.
ARI, diarrhoea, Malaria and Malnutrition
Objectives of IMNCI Strategy Classification Treatment
• To significantly reduce mortality and morbidity Possible serious • Single dose of intramuscular
associated with the major disease in children. bacterial infection ampicillin and gentamicin to
• To contribute to healthy growth and development of or not able to be given
children feed or severe
IMCI vs. IMNCI malnutrition
• During the mid-1990s, the World Health Severe • Follow Plan C (Start IV fluid
Organization (WHO), in collaboration with UNICEF dehydration immediately. Give ORS by
and many other agencies developed IMCI strategy mouth if child can drink. 100 ml/
• This strategy has been expanded in India to include all kg Ringer’s Lactate Solution or
neonates and renamed as IMNCI (RCH phase II (2005) normal saline to be given)
• Close to 50 per cent of newborn deaths in India occur Severe persistent • Single dose of intramuscular
during the first seven days of birth diarrhea and ampicillin and gentamicin
Highlights of IMNCI severe dysentery if the young infant has low
weight, dehydration or
• Inclusion of 0 – 7 days old baby another severe classification
• Incorporating national guidelines on malaria,
anemia, vitamin-A supplementation, and Jaundice • Give care at home for the young
immunization schedule infant.
• Educate the mother when to
• Training of health personnel –time and content equal
return immediately.
for both age categories
• Follow up in 2 days
• Skill based
Some dehydration • Plan B (treat with ORS
Key features
according to weight)
• Syndromic approach
• Holistic approach No dehydration • Follow plan A (Counsel the
mother on the 3 Rules of
• Triage
Home Treatment: Give Extra
• Standardized case management Fluid, Continue Feeding,
• Primary health care model Educate about danger signs of
• Community participation dehydration & when to return)
Principles of management in IMNCI Difficulty in • Appropriate advice about
• Case management procedures based on two age feeding or low feeding
categories: weight for age • Advising mother to treat thrush
j Young infants age up to 2 months at home
j Children age 2 months to 5 years • Follow-up low weight for age in
14 days
Check for possible bacterial infection/jaundice
Assess diarrhoea
Urgent pre-referral treatment of child 2months to 5 yrs
Check for feeding problem, malnutrition and
immunization status Classification Treatment
Check for other problems Severe pneumonia • 1st dose of injectable
Classify conditions and identify treatment actions or very severe chloramphenicol is given
according to colour coded treatment charts disease (or oral amoxicillin)
Pink - Pre-referral treatment + Refer urgently to hospital Very severe febrile • 1st dose of intramuscular
Yellow - Specific treatment at PHC disease quinine after making a blood
Green - Home based management smear
• 1st dose of intravenous
For all infants before referral or intramuscular
• Prevention of hypoglycemia by giving breast milk or chloramphenicol (or oral
sugar water amoxicillin).
• Warming the young infant by ‘skin to skin’ contact • One dose of paracetamol in
if temperature < 36.50C (or feels cold to touch) clinic if child is afebrile (temp
Kangaroo Mother Care during referral to higher centre. 38.5 °C or above)
349
mebooksfree.com
Classification Treatment Classification Treatment

st
Severe • 1 dose of Vitamin A to be Fever-malaria • One dose of paracetamol in clinic
complicated given unlikely for high fever
measles • 1st dose of injectable • Advise the mother when to return
chloramphenicol (or oral immediately
amoxicillin) • Follow-up in 2 days if fever persists
• Apply tetracycline eye • If fever is present every day for more
ointment if eye discharge than 7 days, refer for assessment
present Measles with • Single dose of Vitamin A.
Mastoiditis • 1st dose of injectable eye or mouth • If pus draining from the eye, treat
chloramphenicol (or oral complications eye infection with tetracycline eye
amoxicillin) ointment.
• 1st I dose of paracetamol for • If mouth ulcers, treat with gentian
pain to be given violet.
Severe • Give single dose of Vitamin A. • Follow-up in 2 days
malnutrition Measles • Single dose of Vitamin A
Chronic ear • Dry the ear by wicking
Treatment of sick child 2months to 5 yrs infection • Follow-up in 5 days
Very low • Assess and counsel for feeding
Classification Treatment weight • Advising mother when to return
Pneumonia • Cotrimoxazole or Amoxicillin for immediately
5 days • Follow-up in 30 days.
• Soothing of the throat and relieve Not very low • If child < 2 years old, assess the
the cough with a safe remedy if weight child’s feeding and counsel the
child is 6 months or older mother on feeding
• Advising mother when to return • If feeding problem persists,
immediately follow-up in 5 days
• Follow-up in 2 days • Advising mother when to return
No • Soothing the throat and relieve the immediately
pneumonia- cough with a safe home remedy if Anemia • To give iron & folic acid therapy
cough or cold child is 6 months or older for 14 days
• Educate mother when to return • Assess the child‘s feeding and
immediately counsel the mother on feeding
• Follow-up in 5 days if not • If feeding problem, follow-up in
improving 5 days.
Some • Plan B • Advice mother when to return
dehydration immediately.
No • Plan A • Follow-up in 14 days
dehydration No Anemia • Give prophylactic iron folic acid if
Persistent • Advising the mother on feeding child 6 months or older
diarrhea • Single dose of vitamin A is given
• Oral zinc sulphate 20 mg daily for
14 days. 21.5 Acute flaccid paralysis (AFP)
• Follow-up in 5 days surveillance
Malaria • Oral antimalarials after making a
blood smear
Case definition
• One dose of paracetamol in clinic
for high fever (temp. 38.5 °C or • Sudden onset of weakness and floppiness in any part
above) of the body in a child < 15 years of age or paralysis in
• Educate mother when to return a person of any age in which polio is suspected.
immediately Principles of AFP surveillance
• Follow-up in 2 days if fever persists • All AFP cases must be reported, not just suspected
• If fever is present every day for more polio.
than 7 days, refer for assessment. • Nil reporting to be considered as important as case
reporting.
350
mebooksfree.com
• AFP cases must be reported immediately.

• Nil reports need to be sent weekly, after a thorough 21.6 Child neglect and abuse
search.
• With improved surveillance more AFP cases will be Definition: WHO defines child abuse or mal-treatment as
reported (Polio & non polio) forms of physical, emotional ill-treatment, sexual abuse, ne-
• Reporting of more cases is a sign of improved glect or commercial exploitation that results in potential harm
surveillance and not failed eradication to the child’s health, survival, development or dignity in the
• It is needed to assure successful eradication of polio context of a relationship or responsibility, trust or power. The
in the shortest possible time term refers to mal-treatment (physical, sexual or emotional)
Steps of AFP surveillance of children by the parents, guardians or other caretakers.
• Establishment & maintenance of Reporting Network Classification of child abuse
• AFP case notification by reporting units • Physical abuse is caused by caregiver’s acts that cause
• AFP case investigation physical harm or have the potential to harm.
• Stool specimen collection & transportation • Sexual abuse applies when child can be used for
• Search for active cases in community sexual gratification.
• Outbreak response Immunization • Emotional abuse occurs when there is failure of
• Follow-up for 60 days caregiver to provide an appropriate and supportive
environment.
Transportation and storage
• Neglect: Failure of parent /guardian to provide for
• Specimen container should be packed in a plastic the development of the child, where he/she is in a
sealed bag.
position to do so, in one or more following areas:
• Whenever possible both specimens from one case to Health, education, emotional development, nutrition,
be packed in a single carrier.
shelter and safe living conditions.
• Temperature <8 °C – stool carrier/vaccine carrier
having 4 fully frozen ice packs at –20 °C. Remember: Neglect should be distinguished from cir-
• Label/paint with different colour cumstances of poverty in that neglect can occur only in cas-
es where reasonable resources are available to the caregiver.
• If delay > 2hrs, store sample in a deep freezer.
Manifestations
• Provision of replacement of ice in case of delay in
hand carried shipments. • Multiple fractures at different stages of healing
• Death can occur due to head injury or injury to
internal organs
• One-third of severely shaken infants die and
majority of survivors suffer from long-term
consequences such as mental retardation, cerebral
palsy or blindness.
• Child exhibit symptoms of infection, genital injury,
abdominal pain, constipation, chronic or recurrent
UTI or behavioural problems.
• Failure to thrive, failure to seek basic health care,
immunisation and deprivation of education and basic
nutrition needs.
Strategies to reduce child abuse and neglect
• Government should ensure that child’s education and
basic right is not exploited
• Paediatricians have significant role in recognising,
responding and reporting child abuse.
• Paediatricians can seek help from Special Juvenile
Police units, Child welfare committees, Child Line,
National and state commissions for Protection of
Child Rights (NCPCR) and NGOs
21.7 Adoption
Definition
Adoption is a legal process by which a child is placed
with a married couple or a single adult who agrees to raise
351
mebooksfree.com
the child as their own and assume all responsibility for • Improve access to primary health care
the child. • Mainstreaming of AYUSH
Who may adopt a child? • To promote healthy life style
• An Indian Core strategies of NRHM
• Non Resident Indian • Decentralization of village and district level health
• A foreign citizen planning and management
• A single female (unmarried, widowed or divorced) or • Appointing ASHA for facilitating the access to health
a married couple services
Laws governing adoption • Strengthen public health delivery services at primary
• Hindu Adoption and Maintenance Act of 1956 and secondary level
(Hindus, Jain, Sikhs or Buddhists) • Mainstreaming AYUSH
• Guardian and Wards Act of 1890 (Foreign citizens, • Improve management capacity to organize health
NRIs and Indian nationals who are Muslims, systems and services
Christians or Jews) • Improve intersectorial coordination
• Juvenile Justice Act of 2000 (a part of which deals with Supplementary strategies
Adoption of children by non-Hindu parents)
• Private partnership to meet national public health
Conditions to be fulfilled by an adoptive parent goals-’public private Partnership’ (PPP)
• Medically fit and financially able to care for a child • Social insurance to raise the health security of poor
• Must be at least 21 years old Goals to be achieved
• No legal upper age limit for parents
• Adoption of the older children, age of the parents National Level Community Level
may be relaxed
• IMR: Decrease to 30/1000 • PHC/CHC should
• Adopted child with special needs, the age limit may • MMR: Decrease to provide good
be relaxed
100/100,000 hospital care.
• If the adoption is of a son, the adoptive father or • TFR: Decrease to 2.1 • Generic drugs at
mother by whom the adoption is made must not • Malaria mortality rate subcentre level
have a son living at the time of adoption. reduction: • Access to UIP
• If the adoption is of a daughter, the adoptive father or j 50% by 2010, additional • Facilities for
mother by whom the adoption is made must not 10% by 2012 institutional
have a daughter living at the time of adoption. • Filaria rate reduction: deliveries
Role of pediatrician j 70%(2010), 80% (2012), • Trained
• Counselling parents about process of adoption. elimination by 2015 community level
• All essential tests such as hepatitis B, HIV with • Dengue mortality rate worker at village
window period are repeated at 3 and 6 months before reduction: level
j 50%(2010) • Health day at
replacement.
• Kala azar mortality rate ANGANWADI
reduction: j Immunization
21.8 National Rural Health Mission j 100%(2010) j Antenatal/
• JE mortality rate postnatal

reduction: check ups
Background
j 50%(2010) • Provision of
• Government of India launched NRHM in 5th April • Cataract operation: Increase house hold toilets
2005 with special focus on 18 states. to 46 lakhs/year 2012 • Improved
• 8 North Eastern States (Assam, Arunachal Pradesh, • Leprosy prevalence rate : outreach services
Manipur, Meghalaya, Mizoram, Nagaland, Sikkim, Reduce from 1.8/10,000 in through MOBILE
Tirupura) plus 8 empowered action group states 2005 to less than MEDICAL UNIT
(Bihar, Jharkhand, MP, Chattisgarh, UP, Uttaranchal, 1/10,000 at district level
Orissa, Rajasthan) were included. • TB DOTS services : 85% Cure • Community
Objectives of the mission rate health insurance
Improve rural health care delivery system • Upgrading CHC to Indian
• To reduce Child and maternal mortality rate Public Health Standards
• Increase utilization of First
• Provide universal access to public health services for
food, nutrition, sanitation and public health services referral units from <20% to
75%
addressing maternal and child health.
• Engaging 250,000 female
• Prevention and control of Communicable Diseases ASHA in 10 states
and Non Communicable Diseases
352
mebooksfree.com
Plan of activities Vitamin A prophylaxis program

A) Creation of ASHA (Accredited Social Health • Implemented in 1970 by The Ministry of Health and
Activist) Family Welfare.
j Health activist in the community • Component of NPCB and RCH.
j 1 ASHA per 1000 population • Priority given for Vitamin A deficient geographical
j Not a paid employee area
j Create awareness about health and its Objective—To decrease the prevalence of VAD from
determinants current 0.6% to 0.5%
j Mobilize community to health care services Beneficiary Group—Preschool children
j Counsel women and escort them to PHC/CHC
and providing medical care for minor ailments • A single massive dose (6 months—1 year—
1 lakh IU, >1 year—2 lakhs I.U.) of vitamin A
B) Strengthening of Sub Centers
(retinol palmitate) orally
j Supply of essential medicines
Strategy
j Provision of MPW/additional ANM
j Provision of funds • Health and nutrition education
C) Strengthening of PHC
• Early detection and proper treatment of infection
j 24 h service in at least 50% of PHC incl. AYUSH • Prophylactic Vitamin A(total 9 mega doses)
practitioner • One additional dose of vitamin A for cases of severe
malnutrition
j Upgradation for 24 h referral service
j Adequate and regular supply of essential drug National programme for the prevention of nutritional
j Strengthening Communicable Disease control anaemia
programme • Launched during 4th 5-year plan
D) Strengthening of CHC’S Objectives
j Maintain ‘Indian Public Health Standards‘ • To assess prevalence of nutritional anemia and give
j Promotion of ‘Rogi Kalyan Samitis’ antianemic treatment
• Iron and folic acid prophylaxis
• Monitoring
21.9 Nutritional programmes • Education
Beneficiaries
related to child health
• Infants between 6 months and 1 year
• Children between 1 and 12 years
Background • Adolescent (12–18years)
• Mainly they are supplementary nutrition programmes • Pregnant women
• Objective: To improve nutritional status in targeted Prophylactic
groups
• Pregnant—One tablet containing 100mg elemental
• To address the specific deficiency diseases through iron and 0.5 mg of folic acid daily for 100 days
various ministries to combat malnutrition
• Children(6–60 months) —one tablet containing
20mg iron and 0.1 mg folic acid daily for 100 days if
Programmes Ministry
clinically anemic
Vitamin A prophylaxis Ministry of Health and • Adolescent girls—One tablet containing 100mg iron
program Family Welfare and 0.5 mg folic acid for 100 days
Prophylaxis against Ministry of Health and • Anemia control through fortification of salt with iron.
nutritional anemia Family Welfare “Triple fortification of salt = iron+ vitamin A + iodine”.
Iodine deficiency disorders Ministry of Health and Special Nutrition Programs
control Program Family Welfare • Started in 1970—under Minimum Needs Program
Special nutrition program Ministry of Social • It covers the urban slums, tribal areas and backward
(SNP) Welfare rural areas
Balwadi nutrition program Ministry of Social • AIM—improve nutritional status of target groups
Welfare • Beneficiaries : Children less than six years, pregnant
and nursing mothers
Integrated child development Ministry of Social
j Children—300 kcal and 10-12 g proteins per day
services Program Welfare
j Mothers—500 kcal and 25 g proteins per day for
Mid-day meal program Ministry of education 300 days per year.
Mid-day meal scheme Ministry of Human ICDS (Integrated Child Development Services)
Resources Development Started in 1975
353
mebooksfree.com
Beneficiaries: Objectives:
• Preschool children <6 years • Attract more children for admission
• Adolescent girls (11–18 years) • Reduce school drop outs
• Pregnant and lactating mothers • Child nutrition
Services are rendered by Anganwadi workers. Principles
• Supplementary nutrition, vitamin A, Iron and folic • Supplement, not a substitute to home meals
acid • Supply 1/3rd total energy requirement and half
• Immunization protein need
• Health check-ups • Reasonably low cost
• Referral services • Easily prepared at school
• Preschool non-formal education for children • Locally available foods used as far as possible
3–6 years • Menu frequently changed
• Nutrition and health education to women
Mid-Day Meal Program Online supplementary materials:
• School lunch program Please visit MedEnact to access chapter wise MCQs and
• Started in 1961 previous year pediatrics theory questions asked in various
• Part of Minimum Needs Program final MBBS University examinations.
354
mebooksfree.com
Index
A Anticholinergics, status BCG Vaccine See Bacillus Calmette

asthmaticus, 115 Guerin (BCG) Vaccine
Abetalipoproteinemia, 101 Anti D-immunoglobulin, idiopathic Bell’s palsy, 288
Absence seizures, 272 thrombocytopenic purpura, 172 Bell’s staging, 80
ACCHD See Acyanotic congenital heart Antidiphtheritic serum (ADS), 135 Benign skin lesions in newborn, 321–323
disease (ACCHD) Anti-TNF agents, juvenile idiopathic Berger’s disease, 251
Acid base disturbances, 35–38 arthritis (JIA), 120 BFHI See Baby-friendly hospital
Acrocyanosis, 321, 322 Aortic regurgitation (AR), 216 initiative (BFHI)
Acrodermatitis enteropathica, 329–330 Aortic stenosis (AS), 215–216 Birth injuries, brachial palsy, 64–65
Acute flaccid paralysis (AFP) Aplastic anemia, 169 Bitot spots, 48
surveillance, 350–351 Arnold Chiari malformation, 269–270 Bleeding approach, to child, 170–171
Acute laryngotracheobronchitis Artemether, malaria, 152 Blood flow, through heart and lungs
(CROUP), 233–234 Artesunate, malaria, 152 after birth, 201
Acute lymphoblastic leukemia (ALL), Arthritis, approach to child, 117–118 Bone age assessment, Tanner/
303–306 Ascites, 196–197 Whitehouse method, 6
Acute myeloid leukemia, 306–309 ASD See Atrial septal defects (ASD) Bone marrow transplantation, 100
Acute respiratory infection (ARI) ASDs See Autism spectrum disorders Brain abscess, 284–285
control programme, 346–348 (ASDs) Brain tumors, 316–317
Acute rheumatic fever (ARF), 218–221 Asperger syndrome, 25 Breast feeding, 39–41
Acyanotic congenital heart disease Astrocytoma, 316 Breath holding spells, 20–21
(ACCHD), 201–202 Atopic dermatitis, 324–325 Bronchial asthma, 110–114
Adaptive immunity, defects, 106–109 Atrial septal defects (ASD), 202–203 Bronchiectasis, 241–242
ADHD See Attention deficit Attention deficit hyperactivity disorder Bronchiolitis, acute, 231–232
hyperactivity disorder (ADHD) (ADHD), 22–23 BSID See Bayley scale of infant
AD inheritance See Autosomal Autism spectrum disorders (ASDs), development (BSID)
dominant (AD) inheritance 23–24
Adolescence, 18 Autistic disorder (AD), 24 C
Adoption, 351–352 Autoimmune hemolytic anemia,
Adrenal corticosteroid biosynthesis 165–166 Cardiac arrhythmia, 227
pathway, 301 Autosomal dominant (AD) inheritance, Cardiac condition, 230
Adrenal insufficiency, 299–300 81, 82 Cardiovascular, involvement in systemic
ADS See Antidiphtheritic serum Autosomal recessive inheritance, 82 diseases, 229
(ADS) Azathioprine, juvenile idiopathic Cardiovascular system, 200–201
Albinism, 93 arthritis (JIA), 120 CCHD See Cyanotic congenital heart
Aldolase B, 96 disease (CCHD)
Alkaptonuria, 93–94 CDH See Congenital diaphragmatic
B
ALL See Acute lymphoblastic leukemia hernia (CDH)
(ALL) Baby-friendly hospital initiative (BFHI), Cerebral palsy (CP), 278–280
Allergic diseases, 109–116 41 CGD See Chronic granulomatous
Allergic rhinitis, 109–110 Bacillus Calmette Guerin (BCG) disease (CGD)
Alpha 1 antitrypsin deficiency, 101 Vaccine, 154 Chediak-Higashi syndrome (CHS),
Ammonium tetrathiomolybdinate, 102 Bacterial infections, 130 104–105
Anemia, approach to child, 158–159 Bayley scale of infant development Child abuse, 351
Anorectal anomalies, 189–190 (BSID), 17 Childhood histiocytosis, 317–318
355
mebooksfree.com
Index
Child neglect, 351 Diarrhoea control programme, Gastrointestinal system, 176–199

Children, vaccines for, 153 345–346 Gastroschisis, 187
Chloroquine, malaria, 152 Diphtheria, 134–135 Gaucher disease, 100–101
Choledochal cyst, 185 Disseminated intravascular coagulation, Genetic counselling, 88–89
Cholera vaccines, 156 172–174 Genetic disorders, 81
Chronic granulomatous disease (CGD), DM See Diabetes mellitus (DM) Genomic imprinting, 84
105–106 Dopamine/norepinephrine hypothesis, Geophagia, 20
Chronic myeloid leukemia (CML), 22 GERD See Gastroesophageal reflux
309–310 Down’s syndrome, 84–86 disease (GERD)
CHS See Chediak-Higashi syndrome Doxycycline, malaria, 152 GHD See Growth hormone deficiency
(CHS) Duchenne muscular dystrophy, (GHD)
Clindamycin, malaria, 152 287–288 Glomerulonephritis (GN), 245
CML See Chronic myeloid leukemia Duodenal atresia, 187 Glomerulonephritis, acute, 245
(CML) Dysentery, 181 Glucose-6-phosphate dehydrogenase
CNS disorders, 76–77 deficiency (G6PD deficiency),
Coarctation of aorta (CoA), 228–229 164–165
E
Cold chain, vaccines, 153 Glycogen storage disorder (GSD),
Congenital adrenal hyperplasia, 300 EBV See Epstein-Barr virus (EBV) 96–97
Congenital aganglionic megacolon, Edward syndrome, 86–87 GN See Glomerulonephritis (GN)
188–189 EIA See Exercise induced asthma (EIA) Gottron papules, 122
Congenital diaphragmatic hernia Emotional deprivation dwarfism See G6PD deficiency See Glucose-6-
(CDH), 79 Psychosocial dwarfism phosphate dehydrogenase deficiency
Congestive cardiac failure (CCF), 221–222 Empyema, 243–244 (G6PD deficiency)
Constitutional growth delay, 10 Enteric fever, 132–134 Graves’ disease, 296–297
Coomb’s test, 159 Enzyme replacement therapy, 100 Growth, 1
Cornea, KF ring, 102 Eosinophilia, 174–175 Growth hormone deficiency (GHD),
Corneal clouding, 99 Epidermolysis bullosa, 327 289–290
Corticosteroids, 113, 328 Epiglottitis (Supra-glottitis), 234–235 Growth velocity, 7
Craniopharyngioma, 317 Epstein-Barr virus (EBV), 141 GSD See Glycogen storage disorder
Crohn disease, characteristic Erythema toxicum neonatorum (GSD)
features, 186 (ETN), 322 Guillian-Barre syndrome, 285–286
CROUP See Acute Exercise induced asthma (EIA), 115–116
laryngotracheobronchitis (CROUP) Exomphalos (omphalocele), 187–188
H
Cushing syndrome, 298–299
Cutis marmorata, 321, 322 Harlequin color change, 321
F
Cyanotic congenital heart disease Hemangioma, 330–331
(CCHD), 207 Factors affecting growth, 1–2 Hematology, 158–175
Cyclophosphamide, 120, 166 Febrile seizures, 270–272 Hematopoietic disorders, 158
Cyclosporine, 120, 166, 250 Feeding, complementary, 41–42 Hematopoietic stem cell transplant
Cystic fibrosis, 243 Ferrous sulfate, 161 (HSCT), 170
Fetal assessment, gestational age Hematuria, approach to, 252
(GA), 55 Hemolytic anemia, approach to child,
D
Fetal circulation, 200–201 162–163
Dandy-walker syndrome, 269 Fever, approach to child, 126–128 Hemolytic uraemic syndrome (HUS),
DDST See Denver developmental Fluid homeostasis, 26–28 250–251
screening test (DDST) F-100 milk-based diet, 47 Hemophilia, 172
Dengue, 147–150 Foreign body aspiration, 239, 240 Hemophilus influenza B vaccine, 154
Dentition, 5–6 Fulminant hepatic failure, 193–195 Hemorrhagic disease, in newborn,
Denver developmental screening test 70–71
(DDST), 17 Henoch-Schonlein purpura (HSP)
G
Development, 13 nephritis, 248–249
Dexamethasone, idiopathic Galactosemia, 95–96 Hepatic encephalopathy, 194
thrombocytopenic purpura, 172 Gastric peristalsis, visible, 177 Hepatic/liver glycogenoses, 96
DI See Diabetes insipidus (DI) Gastroesophageal reflux disease Hepatitis A, vaccine, 157
Diabetes insipidus (DI), 290–291 (GERD), 177–178 Hepatitis B, chronic, 193
Diabetes mellitus (DM), 291–294 Gastrointestinal bleeding, lower, Hepatitis B, vaccines, 156–157
Diabetic mother, infant of, 65 approach to child, 191 Hereditary fructose intolerance, 96
Diaper dermatitis, 325 Gastrointestinal bleeding, upper, Hereditary spherocytosis (HS),
Diarrhea, chronic, 183–184 approach to child, 190–191 163–164
356
mebooksfree.com
Index
HIE See Hypoxic ischemic J Meningococcal vaccine, 156

encephalopathy (HIE) Mental retardation/intellectual
Hirschsprung disease, 188–189 Jaundice, neonatal, 67–70 disability, 280–281
Hirschsprung enterocolitis, 188 JIA See Juvenile idiopathic arthritis (JIA) Metabolic acidosis, 35–36
HIV, in children, 145–147 Juvenile dermatomyositis, 122–123 Metabolic alkalosis, 36–38
Hodgkin lymphoma, 310–311 Juvenile idiopathic arthritis (JIA), Metabolic disorders, 90–102
Homocystinuria, 94–95 118–120 Methotrexate, 120, 161, 305
Horner syndrome, 65 Microcephaly, 12–13
HS See Hereditary spherocytosis K Microcytic hypochromic anemia, causes
(HS) of, 159
HSCT See Hematopoietic stem cell Kangaroo mother care (KMC), 66–67 Milia, 323
transplant (HSCT) Kawasaki disease, 123–124 Miliaria, 322–323
HUS See Hemolytic uraemic syndrome Kerosene poisoning, 336–337 Milk, nutritional composition, 40
(HUS) Kidney disease, chronic, 262–263 Milk, types of, 39
Hydrocephalus, 267–269 Kidney injury, acute, 260 Minimal change disease/steroid
Hydroxychloroquine, 122, 123 Klinefelter syndrome, 87–88 sensitive nephrotic syndrome,
21-Hydroxylase deficiency, 301–302 KMC See Kangaroo mother care (KMC) 253–256
Hyperglycemia, 65, 78, 97 Kwarshiorkar, 44 Mitochondrial disorders, 84
Hyperkalemia, 33–34 Mitochondrial inheritance, 84
Hypernatremia, 32 L Mitral regurgitation (MR), 214–215
Hypersegmented neutrophils, 162 Mitral stenosis, 213–214
Hypertension, 222–223 LAD See Leukocyte adhesion defect MMR See Mumps measles rubella
Hyperthyroidism, 296–297 (LAD) (MMR)
Hypocalcemia, 34–35 Langerhans cell histiocytosis (LCH), Molluscum contagiosum, 325
Hypoglycemia, 77 318 Mongolian spots, 322, 323
Hypokalemia, 32 Laws of growth, 2 MPS See Muco-polysaccharidoses
Hyponatremia, 28–29 LCH See Langerhans cell histiocytosis (MPS)
Hypoparathyroidism, 297–298 (LCH) Muco-polysaccharidoses (MPS), 98–100
Hypophosphataemia, 47 Lead poisoning, 337–338 Multifactorial inheritance, 83
Hypothermia, 65–66 Leflunomideand hyroxychloroquine, Mumps, 143–144
Hypothyroidism, 294–296 juvenile idiopathic arthritis Mumps measles rubella (MMR), 155
Hypoxic ischemic encephalopathy (JIA), 120 Myasthenia gravis, 286
(HIE), 76–77 Leptospirosis, 137–138 Myeloperoxidase (MPO) deficiency, 105
Leukocyte adhesion defect (LAD), 104
Levothyroxine, for hypothyroidism,
I 9, 295
N
Idiopathic hypertrophic pyloric Liver abscess, 191–192 Nagele’s rule, 55
stenosis, 176–177 Liver disease, chronic, 195–196 National immunization schedule,
Idiopathic thrombocytopenic purpura, Liver failure, acute in children, 195 vaccines, 153–154
171–172 Liver transplantation, 102, 196 National programme for the
IgA nephropathy, 251 Lung abscess, 240–241 prevention of nutritional
Immunity, classification, 103 anaemia, 353
Immunodeficiency diseases, 103 National Rural Health Mission,
M
Infant botulism, 286–287 352–353
Infectious diseases, 126–157 Macrocephaly, 12–13 Necrotizing enterocolitis, 79–80
Infectious mononucleosis, 141–142 Macrocytic hypochromic anemia, Neonatal Grave’s disease, 79–80, 296
Infective endocarditis, 223–226 causes of, 159 Neonatal jaundice, 67–70
Inflammatory bowel disease, 186 Magnesium sulfate, patient evaluation Neonatal resuscitation, 60–62
Innate/natural immunity, defects, with chronic diarrhea, 184 Neonatal sepsis, 71–72
104–106 Malabsorption, 185–186 Neonatology, definitions, 59–60
Integrated Child Development Services Malaria, 150–152 Nephritic syndrome, acute, 245
(ICDS), 353 Malnutrition, severe, 45–47 Nephritis immune complex
Integrated management of neonatal Maple syrup urine disease (MSUD), 95 deposition, 246
and childhood illness (IMNCI ), Marasmus, 44–45 Nephrology, 245–265
348–350 Measles, 142–143 Nephrotic syndrome, 253–257
Intravenous immunoglobulin, 109 Mechanic’s hands, 122 Neural tube defects (NTD), 266–267
Intussusception, 184–185 Medulloblastoma, 317 Neuroblastoma, 314–315
Iron deficiency anemia, 160–161 Mefloquine, malaria, 152 Neurocutaneous syndromes, 274–276
Iron poisoning, 338–339 Megaloblastic anemia, 161–162 Neurofibromatosis, 274–275
357
mebooksfree.com
Index
Neuromuscular system, disorders Poststreptococcal glomerulonephritis S

of, 285–288 (PSGN), 245–247
Newborn, surgical diseases of, 79–80 Potassium, 32–34 Savant syndrome, 24
Nitisinone (NTBC), 93, 94, 195 Prednisolone, 113, 172 Scabies, 324
Nocturnal enuresis, 22 Pregnant women, vaccines, 154 Scorpion sting, 342–344
Non-hodgkin leukemia, 311–313 Prenatal diagnosis, gestational age Scrub typhus, 135–136
Normocytic normochromic anemia, (GA), 55 Seizures, 270
causes of, 159 Primaquine, malaria, 152 Severe malnutrition, management of,
Nutritional programmes related to Protein energy malnutrition (PEM), 45–47
child health, 353–354 42–43 Shake test, 73
Nutritional recovery syndrome, 47 Pseudotumor cerebri (Idiopathic Short stature, 7–9
intracranial hypertension), 277–278 Sickle cell, 168–169
PSGN See Poststreptococcal Simian crease, 85
O Skin functions, 321
glomerulonephritis (PSGN)
Obesity, 11–12 Psychosocial dwarfism, 10 Skin physiology, 321
Obstructive emphysema, 240 PUO See Pyrexia of unknown origin SLE See Systemic lupus
Omphalocele, 187–188, 319 (PUO) erythematosus (SLE)
Pyoderma, 326–327 Slit lamp examination, 102
Pyrexia of unknown origin Snake bite, 339–342
P Snowman sign, 212
(PUO), 129–130
Pagophagia, 20 Pyrimethamine, malaria, 152 Staphylococcal infections, 131–141
Paracetamol poisoning, 335–336 Staphylococcal pneumonia, 238–239
Patau syndrome, 87 Staphylococcal scalded skin
Q syndrome, 328–329
Patent ductus arteriosus (PDA),
205–207 Quinine, malaria, 152 Status asthmaticus, 114–115
PDA See Patent ductus arteriosus (PDA) Status epilepticus, 272–274
PDD See Pervasive developmental Steeple sign, 234
R Steroid resistant nephrotic
disorders (PDD)
Pediatric oncology, 303–320 Rabies immunoglobin (RIG), 156 syndrome, 256–257
Pediculosis, 324 Rabies vaccine, 155–156 Steven johnson syndrome, 327–328
PEM See Protein energy malnutrition Raised intracranial tension, 276–277 Strawberry tongue, 124
(PEM) Ramstedt’s pyloromyotomy, 177 Sturge-Weber syndrome, 276
Pentavalent vaccine, 154–155 Rapidly progressive glomerulonephritis Stuttering, 23
Pericarditis, acute, 226–227 (RPGN), 248 S. typhi, multidrug-resistant strains, 133
Peritonitis, 197–198 RD syndrome See Respiratory distress Subacute sclerosing pan-
Persistent diarrhea, 181–183 (RD) syndrome encephalitis, 285
Pertussis, 130–131 Ready to use therapeutic food (RUTF), 47 Subcutaneous fat necrosis of
Pervasive developmental disorders Refeeding syndrome, 47 newborn, 322
(PDD), 23 Renal failure, acute, 260–262 Sulfasalazine, 120, 186
Petitmal seizures See Absence seizures Renal failure, chronic See Kidney Supra ventricular tachycardia, 227–228
Phenyl alamine, 92 disease, chronic Swollen epiglottis, on direct
Phenylketonuria, 92 Renal replacement therapies (RRT), laryngoscopy, 235
Physical growth, assessment of, 2–5 263–264 Sydenham’s chorea, 285
Pica, in children, 20 Renal tubular acidosis, 257–258 Systemic anaphylaxis, 110
Plumbism See Lead poisoning Reproductive and child health Systemic lupus erythematosus
Pneumatocele, right sided, 238 programme, 348 (SLE), 120–122
Pneumatosis, 80 Respiratory distress (RD) syndrome, 73
Pneumococcal pneumonia, 238 Respiratory system, diseases of, 231
T
Pneumococcal polysaccharide vaccine Retinoblastoma, 313–314
(PPSV), 157 Rett syndrome, 25 Takayasu arteritis, 124–125
Pneumococcal vaccine, 157 Rhabdomyosarcoma, 316 Tall stature, 10
Pneumonia, 235–239 Rheumatology, 117–125 TAPVR See Total anomalous pulmonary
Poisoning, 332–335 Riboflavin deficiency, 51 venous return (TAPVR)
Polyarteritis nodosa, 125 Rotavirus vaccines, 155 TB See Tuberculosis (TB)
Polycystic kidney disease, 264 RPGN See Rapidly progressive Temper tantrums, in children, 20
Polygenic inheritance, 83 glomerulonephritis (RPGN) The ten steps to successful
Portal hypertension, 198–199 RRT See Renal replacement therapies breastfeeding, 41
Posterior fossa anomalies, 269–270 (RRT) Terbutaline, status asthmaticus, 115
Posterior urethral valve, 264–265 Ryle’s tube, 137 Tetanus, 136–137
358
mebooksfree.com
Index
Tetracycline, malaria, 152 Tyrosine metabolism, 92 Viral meningoencephalitis, 283–284

Tetralogy of fallot (TOF), 207–209 Tyrosinemia, 92–93 Vitamin A, 47–49
TGA See Transposition of the great Vitamin B6, 52
arteries (TGA) Vitamin B12, 52
U
Thalassemia, 166–168 Vitamin C, 52–53, 94, 116, 161
Theophylline, status asthmaticus, 115 Ulcerative colitis, characteristic features, Vitamin deficiencies, 47–53
Thiamine deficiency, 51 186 Vitamin E, 50
Thrive, failure to, 10–11 Uniparental disomy, 84 Vitamin K, 50, 70–71
Thrombosis, approach to child, 174 Urinary DNPH (2, Vitamin K deficiency bleeding
Tics, 21 4-dinitrophenylhydrazine) test, 95 (VKDB), 70–71
Tonsillopharyngitis, acute, 232–233 Urinary ferric chloride, 95 Von Gierke disease, 97–98
Total anomalous pulmonary venous Urinary tract infections (UTI), 258–259 von Recklinghausen disease, 274
return (TAPVR), 212–213 UTI See Urinary tract infections (UTI) V-sign, 122
Tourette syndrome, 21
Toxic epidermal necrolysis, 328
V W
Transient metabolic disorders, 77–79
Transposition of the great arteries Vaccines, types of, 152 Walk in cold rooms (WIC), 153
(TGA), 210–211 Valvular lesions, 213–214 Watery diarrhea, acute, 178–181
Tricuspid atresia, 211–212 Varicella, 144–145, 157 WIC See Walk in cold rooms (WIC)
Trisomy 21 See Down’s syndrome Varicella Zoster immunoglobulin Wilms tumor, 318–320
Tuberculosis (TB), 138–141 (VZIG), 157 Wilson disease, 101–102
Tuberculous meningitis, 282–283 Vasculitis, 123–125
Tuberous sclerosis (TSC), 275–276 Vein of galen malformation, 269
X
Turcot syndrome, 317 Ventricular septal defect (VSD), 204–205
Turner syndrome, 88 Vesico uretric reflux (VUR), 259–260 X-linked, dominant inheritance,
Ty21a vaccine, 134 Viral hepatitis, acute, 192 82, 83
Typhoid vaccine, 157 Viral infections, 141–150 X-linked, recessive inheritance, 82, 83
359
mebooksfree.com

Pediatrics Arun Babu

Uploaded by

Copyright:

Available Formats

Pediatrics Arun Babu

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pediatrics Arun Babu

Uploaded by

Copyright:

Available Formats

mebooksfree.

Pediatrics for Medical Graduates, 1e, Arun Babu Thirunavukkarasu

Content Strategist: Sheenam Aggarwal

Printed in India by EIH Ltd, Printing Press (Manesar, Haryana)

1. Growth and Development......................................................................................................................................1

Online supplementary materials:

- Multiple pregnancies, medical illnesses,

E. Nutritional factors j Somatic growth curve is “Sigmoid” shaped

c. Over-nutrition and obesity Dormant during entire childhood

j Rapid in later months of pregnancy and early

In >2 years—Stadiometer (Fig. 1.3B)

• Predicted Adult height = (Height at 2 years) × 2

Figure 1.5 Shakir tape.

• Head circumference > chest circumference by 2 cm in

formula fed infants. CDC based on both breast

1.7 Growth charts

• Definition—Charts in which growth parameters

– Cardiopulmonary: Congenital heart disease, j Increase in US:LS ratio—Rickets, achondroplasia,

Figure 1.9 Diagnostic approach to Short stature in Children.

j Intake of balanced diet with macro- and micro-

• Definition: This term includes infants and young

Figure 1.10 Diagnostic approach to Tall stature in Children.

Causes of FTT • Body Mass Index is the best parameter to screen

• Liver function test • Hypertension j Migraine

• BUN, serum creatinine Endocrine • Orthopedic

• Serum calcium, phosphorous, ALP—to rule out rickets mellitus vara)

• Treatment focussed on etiology and associated syndrome problems

• Stimulate the child fatty liver disease j Obstructive sleep apnea

Causes of Microcephaly • Development is a continuous process, starting in

• Chronic • Chronic • Hydrocephalus of the child.

j Others—environmental exposure (lead, mercury,

1.21 Development milestones (Figs. 1.11A–I)

Gross Motor Visual Motor Language Social adaptive

Gross Motor Visual Motor Language Social adaptive

• Development delay = (developmental age/

Figure 1.11 (E) Creeping.

Figure 1.11 (C) Sitting without support.

Figure 1.11 (F) Crawling.

• Developmental quotient = Observed age of

1.23 Red flag signs in child

• Loss of previously attained milestones—Neuro-

1.24 ‘Development assessment’ tests

• Developmental screening tests are designed to

2.1 Adolescence 2.3 Changes during adolescence

• Adolescence is a period in life characterized by

2.2 Stages of adolescence 2.4 Emotional and social changes

• Early adolescence (10-13 years) • Preoccupied with body image

Micronutrient deficiencies like iron deficiency

2.5 Important Health problems anemia, iodine deficiency

2.6 Sequence of changes in puberty

• First visible sign of puberty is the Thelarche. It occurs

• Poor socioeconomic status

Starts separating from primary caregivers

Children can do exactly the opposite of what was

• There are four types: Chronic tic—

j Simple breath holding spell – Motor or vocal tic

Treatment: • Atypical functioning in the frontal lobes, basal

associated with mental retardation, normal

• Pharmacotherapy Clinical features

• Disorder of early brain development