Facu/f

Kasr

KASR A A Nt
Pediatrics Department

PEDIATRICS
For medical
students

Recent guidelines
Updated Information
New topics
PEDIATRICS
FOR MEDICAL STUDENTS

Part 2

Under supervision of

Prof. Dr: Iman Ehsan Abdel Meguid

Professor of Pediatrics &Genetics Chair of
the Pediatrics department Faculty of
Medicine Cairo University

12 th EDITION
PREVIOUS EDITIONS
1st EDITION: Prof. Dr. Abdel Hakim Shehata: 1974
2nd EDITION: Prof. Dr. Safwat Shoukry: 1978
3rd EDITION: Prof. Dr. Hussein Kamel Bahaa Eldin: 1989
4th EDITION: Prof. Dr. Ekram Abdelsalam: 1989
5th EDITION: Prof. Dr. Mohammed Khalil Abdelkahlek:1991
6th EDITION and 7 th editions: Prof. Dr. Fadia Mahmoud: 2003-4
8th EDITION: Prof. Dr. Mona Abouzekri: 2010
9th EDITION: Prof. Dr. Ahmed Elbeleidy: 2013
10 th EDITION: Prof. Dr. Magda Badawy: 2016
11 th and 12th EDITION: Prof.Dr. Iman Ehsan Abdel Meguid: 2017-2018

EDITORIAL BOARD FOR 11 th AND 12™ EDITION

Editor in Chief and Module Coordinator:
Prof. Dr: Iman Eyada

Associate Editor and Designer

Prof. Dr: Mostafa Zakaria

Editor: Prof. Dr: Ahmed

Badr
 Preface to the 12th edition
Pediatrics for medical students presents brief and comprehensive information,
addressing the requirements of the undergraduate curriculum in an interesting manner.
The students will study the fundamentals of Pediatrics and child health as well as have
a thorough knowledge of important diseases of children.

The current 12 th edition has many unique features. The newly introduced colorful
layout and various illustrations, the updated knowledge and recent guidelines make the
book more readable and student friendly. It is a continuation of the effort started by
our late professor AbdelHalim Shehata since 1974.

Contributed by our distinguished professors, all chapters were written and presented in
a uniform and consistent style to facilitate an easy and clear understanding of the
subject.

I would like to express my deep appreciation to Professor Dr.lman Eyada, our

Module Coordinator and Editor-in-Chief, for her enormous efforts and devotion to the
creation of this book.

A special thank you goes to Professor Dr.Mostafa Zakaria for his exceptional efforts
in both editing the contents of this book and designing its layout.

Lastly I would also like to acknowledge Professor Dr.Ahmed Badr for his remarkable
contributions and outstanding work.
Wishing the very best to all our students.

Dr.lman Ehsan Abdel Meguid

Professor of Pediatrics &Genetics
Chair of the Pediatrics department
Faculty of Medicine Cairo University

IV
CONTENTS
1. NEUROLOGY................................................................................1
Revised by Prof.Dr. Omnia Afifi and Prof. Dr. Marian Yousry

2. CARDIOLOGY..............................................................................43
Revised by Prof.Dr. Hala Hamza and Prof.Dr. Fatma Elzahraa Mostafa Gomaa

3. RESPIRATORY........................ 77
Revised by Prof.Dr. Mona Elfalaki and Prof.Dr Mona Mohsen

4. ALLERGY...................................................................................104
Revised by Prof.Dr. Mona Elfalaki and Prof.Dr. Mona Mohsen

5. HEPATOLOGY...........................................................................124
Revised by Prof.Dr. Sawsan Okasha and Prof.Dr. Magd Kotb

6. ENDOCRINOLOGY.....................................................................141
Revised by Prof.Dr. Sherine Abdelghaffar and Prof.Dr. Ghada Anwar

7. NEPHROLOGY...........................................................................155
Revised by Prof.Dr. Bahia Mostafa, Prof.Dr. Fatina Fadel, Prof.Dr. Nevine Soliman,
Prof.Dr. Ahmed Badr

8. HEMATOLOGY..........................................................................184
Revised Prof.Dr. Iman Abedelraouf and Prof.Dr. Ilham Yousryby

9. RHEUMATOLOGY.............................................................218
Revised by Prof.Dr. Hala Salah
 Hydrocephalus

CSF circulation

1. Secretion
Choroid plexus in the
ventricles (lateral ventricle
2. Circulation
mainly)
Lateral ventricle
"P
Foramina of Monro
sk
3rd ventricle
Sp
Aqueduct of Sylvius sP
4th ventricle

Foramen of Luschka and Magendie

sp
Subarachnoid space

3. Absorption

CSF is reabsorbed into venous circulation from subarachnoid spaces by

arachnoid villi

CSF circulation

1
Definition
Dilatation of the ventricular system, due to imbalance between production and absorption of
CSF.

Etiology and types

Obstructive (non- communicating) hydrocephalus

1. Congenital
a. Aqueduct stenosis (the most common congenital cause): congenital stenosis or due to
toxoplasmosis
b. Dandy Walker malformation
Incomplete formation of the cerebellar vermis with obstruction of foramina of Magendia
and Luschka: Cystic expansion of the 4 th ventricle with bulging occiput.
c. Vein of Galen malformation.

2. Acquired (the most common site of obstruction is at the aqueduct of Sylvius)

a. Traumatic: Posterior fossa subdural hematoma
b. Inflammatory post meningitic gliosis
c. Neoplastic: posterior fossa tumors e.g. cerebellar medulloblastoma

Non obstructive (communicating) hydrocephalus

1. Congenital: Arnold- Chiari malformation

There is Failure of pontine flexure developments downward displacement of medulla
and cerebellums obstruction of subarachnoid space around the brain stem usually.
Meningomyelocele is present in 80% of cases.
2. Acquired
a. Traumatic: subarachnoid hemorrhage.
b. Inflammatory post meningitic subdural adhesions
c. Neoplastic: choroid plexus papilloma Soverproduction of CSF

Ski
n

Chiari malformation Spinal

Meningomyeloc
cord
ele

2
Clinical picture

Before closure of sutures and fontanelles (in infancy)

General examination
1. Head examination
• Circumference: progressive increase in all skull diameters.
• Scalp skin: thin and shiny.
• Scalp veins: prominent.
• Anterior fontanelle: widely opened.
• Sutures: widely separated.
• Face: globular and prominent forehead
• Eye:sunset appearance
2. Back For any swellings: meningocele or meningomyelocele in Chiari malformation

Neurological examination in moderate to severe cases

1. Motor system
• Tone: spasticity of limbs (compression on motor area :UMNL) may be hypotonia in the
lower limbs with meningomyelocele)
• Power: for evidence of paralysis.
2. Reflexes: exaggerated.
3. Cranial nerves: squint and optic nerve atrophy may be present.
4. Delayed motor and mental development

3
After closure of sutures (older children)
1. Head enlargement is less evident because sutures do not separate.
2. Neurological
■ Signs of increased intracranial tension are marked
• Variable neurological deficits (spasticity, ataxia...)

Investigations
1. CT scan (the most important): dilatation of the ventricular system
• Obstructive hydrocephalus: dilatation only proximal to the site of obstruction
• Communicating hydrocephalus: all ventricles are dilated
2. Hydrocephalus may be diagnosed on antenatal ultrasound screening.

Dilated lateral ventricles

Differential diagnosis
Causes of large head (see macrocephaly)

Treatment

1. Surgical
a. Removal of cysts or tumors that cause obstruction e.g. (choroid plexus papillectomy)
b. Non removable causes~^shunt operation: ventriculoperitoneal shunt is the

most
common
Shunt complications
• Infection (septicemia and ventriculitis)
• Obstruction, kinking, or separation.
• Shortening with age : as the child grows it is
Valve
replaced by a larger one
2. Acetazolamide: in non-progressive cases
Underneath
The skin

4
 Cerebral Palsy

Definition
It is a non-progressive, non-fatal and non-curable motor deficit.
Other manifestations of organic brain damage (as seizures, mental retardation, sensory and
learning defects with behavior and emotional disturbances may be present)

Etiology
Prenatal causes
1. Cerebral malformations
2. Congenital infections (TORCH infections)
3. Severe intrauterine fetal anoxia.

Perinatal causes
1. Hypoxic ischemic injury.
2. Intracranial Hemorrhage.
o Prematurity is not a cause but frequently associated with asphyxia and
intracranial hemorrhage.

Post- natal causes

1. CNS infections: meningitis and encephalitis.
2. Severe Hypoxia: asphyxia and status epilepticus
3. Intracranial Hemorrhage.
4. Metabolic: hypernatremia and hypoglycemia
5. Kernicterus

Clinical diagnosis: initial findings are vague till development delay become evident.

Early features of cerebral palsy

1. Motor delay
2. Microcephaly (or slowing of head growth).
3. Moro reflex and other primitive reflexes persistence.
4. Abnormal limb or trunk posture
5. Asymmetric hand functions.
6. Feeding difficulties: slow feeding and gagging ( pseudobulbar)
7. Floppy infant at birth or early infancy.

5
Clinical Types of cerebral palsy: Spastic, Dyskinetic, Ataxic and Atonic

A. Spastic cerebral palsy: 70% of cases

• It is due to damage of cerebral motor cortex or its connections
■ Examination of motor system and reflexes reveals:-
1. State: wasting due to disuse atrophy.
2. Power: paresis (quadriplegia, hemiplegia or diplegia).
3. Tone: spasticity: clasp knife affecting antigravity muscles.
4. In the upper limbs: biceps, pronators -> flexed arm and forearm with fisting of the hands
In the lower limbs: adductors and hamstrings -> (extension and scissoring), calf
muscles-> ankle clonus.
5. Reflexes: deep reflexes are exaggerated and planter reflex is positive.

According to the power (degree of motor area damage) spastic CP is classified into
4 types

1. Quadriplegic
• Paresis affects both sides of the body (upper limbs and lower limbs).
• The arms are affected equal to or more than the legs.
It is often associated with seizures, microcephaly, pseudobulubar affection and
moderate or severe intellectual impairment.
• History of hypoxic-ischemic encephalopathy at birth is usually present.

2. Hemiplegic
• Paresis affects one side of the body.

6
 • The arm is usually affected more than the leg
• Fisting of the affected hand and spared face

3. Diplegic
• Paresis affects both lower limbs with arms are less affected or not affected

4. Monoplegic: only one limb is affected usually an arm

B. Dyskinetic (dystonic or athetoid) cerebral palsy: 10% of cases

• It is due to damage in the basal ganglia or its associated pathways (extrapyramidal)
• Examination

Irregular involuntary movements of some or all muscle groups:

• Athetosis is the commonest associated abnormal movement; it is
purposeless snake like distal movement.
Dystonia (simultaneous contraction of the agonist and antagonist muscles involving
the trunk or proximal limbs) may also present.
Hypotonia and poor trunk control

Athetosi
s

C. Ataxic cerebral palsy: 10% of cases.

1. It is due to damage in the cerebellum.
2. Presents with hypotonia, lack of coordination and intention tremors.
D. Atonic cerebral palsy (cerebral infantile hypotonia) 10% ofcases
1. Floppy infant like picture, hypotonia of the trunk and neck muscles are severe.
2. Deep reflexes are preserved and even exaggerated.

7
Degree of functional disability
1. Classi: no limitation of activity
2. Class II: slight to moderate limitation
3. Class III: moderate to great limitation
4. Class IV: no useful physical activity

Complications and association

1. Muscle wasting with joint deformities and contractures
2. Recurrent aspiration and chest infection
3. Associations: mental retardation, epilepsy, squint and cranial nerve palsies

Investigations: see mental retardation

1. CT brain - MRI brain
• May determine the location and extent of structural lesion.
• May show associated malformations or brain atrophy.
2. EEG
3. TORCH screening to define the cause
4. Auditory assessment and VEP:( visual evoked potential)

Diagnosis should include the following

1. Etiology of cerebral palsy e.g. posts hypoxic cerebral palsy.
2. Type of cerebral palsy e.g. spastic, dyskinetic, ataxic, mixed and cerebral hypotonia.
3. Associated findings e.g. motor (wasting), cranial nerves (bulbar) and microcephaly.
4. Associated deficits e.g. mental retardation, epilepsy and deafness.
5. Degree of functional disability

Differential diagnosis
1. Other causes of floppy infant (see later)
2. Other causes of spasticity as degenerative brain diseases e.g. leukodystrophies
3. Other causes of ataxia or cerebellar anomalies

Treatment rehabilitation
1. Physiotherapy.
2. Positioning and splints to prevent contracture.
3. Associated complications and neurological problems as
a. Epilepsy: antiepileptic drugs
b. Orthopedic management: Tendon releases in contracture
c. Treatment of chest infection
d. Special feeding program

8
 Intellectual Disability

Definition
Intellectual disability (ID) previously called mental retardation, is a generalized
neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive
functioning. Mental retardation is not a diagnosis, it is rather a symptom and its etiology has to
be reached.

Grading
Mental age
According to I.Q (intelligence quotient) = Chronological age x
|qq
1. Mild I.Q between 75-50% Educable: (85 to 90%
of cases)
2. Moderate 50-35%
Trainable
3. Severe 35-20%
Non- trainable
less than 20
4. Profound % Non- trainable

Etiology

Hereditary causes
1. Chromosomal abnormalities
• Trisomy: Down syndrome- Edward syndrome
• Deletion: Prader Willi syndrome
• Sex chromosome: fragile X syndrome.
2. Genetic microcephaly
Primary microcephaly (Autosomal recessive)
2. In born errors of metabolism e.g.
• Phenylketonuria
• Homocystinuria Phenylketonu
ria

3. Neurodegenerative brain disorders e.g. Rett syndrome

Acquired causes

1. Prenatal (intrauterine)
• Cerebral malformations (hydranencephaly)- Cerebral dysgenesis
• Congenital infections (Cytomegalovirus, Rubella, Toxoplasmosis)
• Severe intrauterine fetal anoxia
2. Perinatal
• Hypoxic ischemic injury.
• Intracranial Hemorrhage.
o Prematurity is not a cause but frequently associated with asphyxia and
intracranial hemorrhage

9
3. Postnatal
• CNS infections: meningitis and encephalitis.
• Severe Hypoxia: asphyxia and status epilepticus
• Intracranial Hemorrhage.
• Metabolic : hypernatremia and hypoglycemia
• Kernicterus
• Lead poisoning

x Congenital hypothyroidism and phenylketonuria should not be causes as they should be

diagnosed by routine screening tests and treated before causing mental retardation.
x Unknown cause in 25% of cases of mental retardation.

Clinical presentations
One of the first signs is delay in receptive and expressive language development. No mama -
dada - baba by 12 months is a red flag sign.

Investigations
Laboratory
1. Karyotyping if a chromosomal abnormality is suspected or if the child is dysmorphic
2. TOTCH screening for the mother and the child
3. Metabolic screening e.g. blood lactate -plasma amino acids - ammonia
4. Urine : amino acids - organic acids
5. Thyroid function tests.

Imaging
1. Cranial ultrasonography, CT or MRI to determine the degree of structural abnormalities of
the brain (brain atrophy, intracranial calcifications with toxoplasmosis and CMV)
2. EEG.
3. Skeletal survey.
Hearing and vision assessment
1. Visual evoke potential
2. Auditory brain stem response (ABR).

Management

Preventive measures

1. Prevention of Congenital Infections e.g. vaccination against rubella

2. Avoid alcohol ingestion during pregnancy
3. Proper antenatal care and proper management of delivery to avoid birth injures

10
General measures
1. Therapeutic program must begin as early as possible with the parents playing an active role
together with the doctor and social workers.
2. Children with IQ ranging from 50-70 could achieve some independence ,while those with IQ
below 50 are rarely independent

Specific measures
1. Dietary measures
Dietary manipulation in inherited disorders as in: Phenylketonuria e.g. Phenylalanine free
formula
2. Physiotherapy and orthopedic measures to preserve muscle bulk and prevent
deformities
3. Speech therapy in case of hearing loss, mental retardation and lack of coordination of tongue
and palate.
4. Ophthalmoscopic assessment
• Visual impairment may be due to optic atrophy or visual cortical damage
• Squint may be due to external ocular muscles imbalance or paralysis.
5. Drug therapy -> antiepileptic drugs (epilepsy occurs in 30% of cases).
6. Educable child should go to special education institutes

1
1
 Seizures

Definition
A transient occurrence of signs and/or symptoms resulting from abnormal excessive or
synchronous neuronal activity in the brain.

Etiology
Epilepsy

Acute symptomatic
seizures

A. Epilepsy

Definition
A disorder of the brain characterized by a predisposition to generate seizures and by the
neurologic, cognitive, psychologic and social consequences of this condition. The clinical
diagnosis of epilepsy usually requires the occurrence of at least 2 unprovoked epileptic
seizures.
Etiology
1. Idiopathic (or cryptogenic): 80% the etiology is not determined.
2. Secondary: 20%
a. Cerebral deformation/ malformation.
b. Cerebral damage: e.g.
■ Congenital infections
■ Hypoxic-ischemic encephalopathy
■ Ischemic stroke,
■ Intracranial hemorrhage
■ Brain tumors
■ Traumatic injury sequelae,
• CNS infections sequelae.
c. Neurodegenerative disorders: loss of previously acquired milestones
d. Neurocutaneous syndromes: Tuberous sclerosis, Neurofibromatosis, and Sturge Weber
syndrome
3. Reflex seizures: usually precipitated by sensory stimuli such as flashing light.
4. Epilepsy syndromes:
A disorder that manifests 1 or more specific seizure types and has a specific age of onset
and specific prognosis

B. Acute symptomatic seizures

Seizures are related to a specific cause and will stop following its treatment as in:-

12
1. CNS infections: Meningitis and encephalitis
2. Metabolic causes: Hypoglycemia - Hypocalcaemia- Hypomagnesaemia -
Hyponatremia - Hypernatremia
3. Head trauma
4. Brain edema
5. Poisons and toxins.

Classification of seizures
The following is the ILAE (International League against Epilepsy) 2010 classification of -
seizures, according to seizure semiology

Generalized Focal Unknown

(partial)
1. Absence (Typical, atypical, Without impairment of consciousness r
1.
absence with special features) or awareness: with observable motor,
Epileptic
2. Generalized tonic-clonic autonomic components
3. Myoclonic (Myoclonic, spasms
2. With impairment of consciousness or
myoclonic atonic, myoclonic awareness (Dyscognitive)
tonic) May evolve to
4. Clonic 3. Bilateral convulsive (secondary
5. Tonic generalized)
6. Atonic

A. Generalized seizures

1. Absence
Preictal:
no aura
Ictal:
There is cessation of motor activity or speech with blank facial expression for 5
to 20 seconds then continuation of the original activity as if nothing happened.

• The attack can be triggered by hyperventilation for a minute.

Postictal: no postictal manifestations
x EEG : characteristic EEG finding: 3 spike/second
x wave
Etiology: idiopathic or genetic
x
Prognosis: good prognosis.

13
2. Generalized tonic clonic
• Preictal: aura e.g. headache or flashes of light
• Ictal
■ Sudden loss of consciousness and falling.
■ Tonic phase
With loss of consciousness, limbs are extended, eyes are rolled up and the head is
thrown backward or to one side. Cyanosis of the face, biting the tongue and
cessation of respiration occur
Clonic phase
Respiration returns, with repetitive contraction and relaxation of all muscles.
Salivation and micturition may occur during this phase
It lasts for few minutes, If it exceeds 30 minutes, the term status epilepticus is
given
x Postictal: deep sleep for hours

■ Ictal
Sudden shock-like jerks affecting predominantly flexor or extensor. Mild
attacks take the form of sudden head drops
. Severe attacks may suddenly throw the child forwards or backwards.
Risk of injury of a part of the body
■ Etiology: mainly symptomatic (2ndry) or
idiopathic

4. Atonic
• These attacks start suddenly by a synchronous increase in muscle tone or brief myoclonic
jerking followed immediately by loss of postural tone and falling to the ground.

B. Partial focal seizures

1. Focal sensory seizures (initiating from occipital and parietal lobes)
2. Focal motor seizures (clonic motor, tonic motor, with automatisms)
3. Secondary generalized seizures (bilateral convulsive)
Formerly focal (partial Jseizures were calssified as Simple or Complex according to the
conscious level during the attacks, if retained it is simple , if impaired it is complex

14
C. Unknown
Epileptic spasms (formerly Infantile Spasms)
• Infants only: 3-8 months of age.
■ Ictal
• Usually occur in clusters lasting for 15-30 minutes, several times per day.
• Sudden flexion ,extension or mixed extension-flexion symmetric contractions of the
neck, trunk and limbs that is more sustained than myoclonic jerk
■ Loss of intellectual functions occurs at the onset of the spasms in most cases
■ EEG is diagnostic: hypsarrythmia
■ Resistant to antiepileptic therapy but it responds to corticosteroids or Vigabatrin.

Clinical evaluation of a case of convulsions

History
1. Did the child have a seizure before?
2. Character of Seizures:
- Type (tonic, clonic, absence, myoclonic) - How many times
- Distribution (focal or generalized) - Duration (brief or prolonged)
- Triggers: head trauma, CNS infection. -Treatment

3. Etiology of seizures
Manifestations of CNS infection (fever, vomiting, loss of consciousness)
History of trauma
Intellectual deterioration-^ degenerative brain disorders
Vomiting, failure to th rive -> inborn errors of metabolism
4. Treatment history (prior anticonvulsant medication and the child's response)

Examination (directed to search for organic cause)

General
1. Vital signs: blood pressure, temperature
2. Measurements: head circumference: microcephaly with congenital infections
3. Trunk and limbs: skin lesions in neurocutaneous syndromes e.g. cafe au lait patches
Systems
1. Neurological examination
■ Level of consciousness
■ Motor and mental development.
■ Signs of increased intracranial pressure
■ Signs of meningeal irritation.
■ Motor, Reflexes, sensations and cranial nerves examination.
■ Fundus examination :papilledema with increased intracranial tension
2. Abdominal examination: organomegaly may suggest metabolic or storage disorders

15
Investigations of seizures
Laboratory
1. Blood picture.
2. Blood chemistry: Na - K - Ca, urea, creatinine and fasting plasma glucose
3. CSF analysis if CNS infection is suspected.
4. Screening for inborn errors of metabolism(Aminogram and TMS)
5. TORCH screening, if clinically indicated (microcephaly, recurrent seizures, cataract),
Imaging
1. EEG
It is done during normal or induced sleep or with activation procedures as hyperventilation
or photic stimulation.24-hour ambulatory EEG done in some cases.
2. CT and MRI if intra-cranial lesion is suspected (increased tension or focal deficit)
3. PET scan (positron emission tomography)

Treatment of
epilepsy_________________
A. Rules in long term antiepileptic therapy
1. Choice of drugs according to clinical and EEG findings.
2. Number of drugs: start with one drug (monotherapy) in small dose (to avoid toxicity,
improve compliance and reduce the cost). A second drug is added (polytherapy) if the
first drug failed to control seizures.
3. Dose: start with an average dose and gradual increase till seizure control.
4. Do not risk toxicity to ensure control.
5. Drug levels a useful method to check compliance of some drugs
6. Duration of therapy: at least 2or 3 years after the child being seizure free
7. Termination of therapy: very gradual (status epilepticus develops with sudden
termination)
8. Ketogenic diet is a recent mode of therapy following failure of response to more than 3
drugs in different regimens

B. Antiepileptic drugs

16
 Drug Seizure type Dose (mg/
kg/day)
1. Sodium valproate - Generalized seizures: 10-40
Tonic clonic, Absence and myoclonic
- Partial seizures
2. Carbamazepine - Partial seizures: the best in partial 10-30
seizures
- Generalized tonic clonic
3. Phenobarbitone
- Generalized tonic clonic and partial 3-5
seizures
4. Phenytoin
as phenobarbitone 5-8
5. Clonazepam
- Myoclonic and epileptic spasms 0.01-0.1
6. Ethosuximide
-Absence and Myoclonic 20-40
7. Vigabatrin
- Epileptic spasms (infantile spasm) 40-80
8. Lamotrigine
- Broad spectrum-Atypical absence seizures 5-10
9. Topiramate
- Resistant partial seizures 5-10
10. Levetiracetam
- Partial, generalized or myoclonic seizures 15-50
10. Corticosteroids - Epileptic spasms, myoclonic seizures
and ACTH - Symptomatic intractable seizures

C. Parents counseling
Children with idiopathic epilepsy should
1. Attend regular schools.
2. Avoid watching TV except in lighted room and far enough from the screen.
3. Computer games and swimming should be done under strict supervision

17
Status epilepticus

Definition
Status epilepticus is a seizure lasting more than 5 minutes or when repetitive seizures occur
without regaining consciousness between them.

Etiology
1. Status epilepticus in the epileptic patient
2. Acute brain insult
o CNS infections
o Intracranial hemorrhage
o Hypoxic encephalopathy
o Metabolic encephalopathy
3. Prolonged (complex or atypical febrile) convulsions

Complications
1. Respiratory: apnea, airway obstruction, pulmonary edema, aspiration pneumonia
2. Neurological: cerebral ischemia, edema, hemorrhage and damage
3. Cardiovascular: shock, heart failure, hypertension and cardiac arrest
4. Metabolic: hyperpyrexia, metabolic acidosis, hypoglycemia, hyponatremia

Treatment of the ongoing seizures or treatment of status epilepticus.

First aid measures: ABC

1. A: Open the airway
2. B: Breathing support and oxygen therapy
3. C: Insert IV line and start infusion of ringer lactate or saline
Immediate anticonvulsant drugs to stop convulsions
1. Diazepam 0.5 mg/kg slow IV or rectal, if not controlled within 10 minutes, give
2. Phenobarbitone 15-20 mg/kg slow IV (loading dose)
5 mg/kg/d (maintenance dose) after seizure control
If phenobarbitone failed to control the seizures within 10 minutes, shift to
3. Phenytoin: 15-20mg/kg slow IV (loading dose)- 5mg/kg/day(maintenance) after seizure
4. If not controlled, transfer to ICU
■ First line: diazepam or midazolam constant infusion.
• Second line anticonvulsants: Levetiracetam IV 60 mg/kg.
• Other drugs: paraldehyde, lidocaine, thiopental
• Usually this requires mechanical ventilation to insure adequate oxygenation and
ventilation.
5. Multisystem support
6. Treatment of the cause

18
Febrile Convulsions

Definition
It is a very common condition which occurs in 5 % of normal children due to rapid rise of body
temperature due to extracranial infections e.g. tonsillitis,

Incidence
■ Between 9 month and 5 years
■ Genetic susceptibility (Positive family) history
■ Male are more affected than females

Evaluation
1. Convulsions occur at the onset of rise of body temperature.
2. Evident extracranial Infection: Usually URTI or gastroenteritis
3. Exclude features of CNS Infections
4. Exclude other causes of seizures (trauma - toxins)
5. If we cannot exclude CNS infection: CSF examination is a must

Then differentiate between:

Simple Febrile seizures: 80% Complex Febrile seizure: 20%

Pattern Generalized tonic clonic May be focal

Duration 5-15 minutes It may persist > 15 minutes

Course Usually 1 convulsive fit Short Recurrent during the same

postictal stupor illness, prolonged postictal
Family hist. Febrile convulsions Epilepsy may be present

Development Normal +/- neurological abnormalities

Treatment
1. Immediate first aid measures
a. Patent Airway ( keep on side+ 100% oxygen)
b. Anticonvulsant drugs (IV or rectal Diazepam: 0.5 mg/kg)
2. Measures to lower the temperature
a. Tab water fomentations
b. Antipyretics e.g. Paracetamol : 10-15 mg/kg/dose
3. Treatment of the cause e g. antibiotics for acute tonsillitis.
4. Long term anticonvulsants are controversial may be given in
a. Persistent EEG abnormality
b. Atypical (complex) febrile convulsion
c. Interval less than 3 months between attacks (sodium valproate 1st choice)

19
Conditions that mimic Seizures
There are multiple conditions which could have a similar picture mimicking seizures, leading
to the misdiagnosis of epilepsy, which is estimated to be as high as 5-40%.

1. Apnea

It can be differentiated from seizures by

■ Apneic episodes in neonates are usually associated with bradycardia. In contrast, apnea
associated with seizures is usually accompanied by tachycardia.
■ However, severe apnea of any cause can be followed by anoxic seizures.

2. Neonatal jitteriness: see neonatology

3. Breath holding spells

Cyanotic, or "blue," breath-holding spell Pallid breath holding spell

Age Incidence: Spells usually begin between 6 and 18 month of age

Etiology
Prolonged expiratory apnea. Reflex vagal-cardiac bradycardia and
asystole

Pathophysiology : immaturity of the autonomic nervous system

Triggered by
Becoming frustrated or angry
Sudden fright or pain or falling with mild
injury
Clinical picture of the spell
■The child may cry vigorously less than 15
seconds ■The child becomes pale(pallid) losses
■ After crying the child becomes silent consciousness and become limp
Stops breathing and rapidly turns blue ■ The child may stiffen and have few jerks
■ Reflex anoxic seizures may follow the
more-severe episodes
1

Duration :
Recovery happens in less than one minute

Management
■ Education and reassurance of the parents as the condition is selflimited and
disappears within few years
■ Treatment of coexisting iron deficiency is needed if it is present as the spells are made
worse by iron-deficiency anemia

20
4. Benign sleep myoclonus and neonatal sleep myoclonus
Clinical picture
■ Repetitive, usually bilateral rhythmic jerks involving the upper and lower limbs during non-
rapid eye movement sleep
■ Sometimes mimicking clonic seizures.
It can be differentiated from seizures by:
1. The lack of autonomic changes
2. It occurs only during sleep
3. It is suppressed by awakening.
Prognosis
x Remission is spontaneous at 2-3 months of age.
x In older children and adults, sleep myoclonus consists of random myoclonic jerks of the
limbs

5. Motor tics
Clinical picture
Sudden, fast, repeated movements e.g. excessive blinking
It can be differentiated from seizures by:
1. They are under partial control, and are associated with an urge to do them and with a
subsequent relief.
2. They are usually exacerbated by emotions, and often change in character over time.

6. Sandifer syndrome:
x Sandifer Syndrome is a pediatric manifestation of gastro-esophageal reflux
Clinical picture
1. Paroxysmal episodes of generalized stiffening and opisthotonic posturing

that may be accompanied by apnea, staring, and minimal jerking of the

extremities.
It can be differentiated from seizures by
1. Episodes often occur 30 min after a feed.
2. History of recurrent vomiting

3. In older children, this syndrome manifests with episodic dystonic or dyskinetic

movement
s.
7. Daydreaming
x It is staring with thinking in a series of pleasant thoughts that distract one's attention from
the present.
It can be differentiated from absence seizures by
1. It occurs only in certain settings (e.g., school)
2. The child responds to stimulation such as touch
3. It doesn't occur while the child is playing.

21
 Meningitis

Definition
Inflammation of the pia and arachnoid matter which might intervene with CSF circulation

Etiology

1. Bacterial
a. During the first 2 months of life
• B P hemolytic streptococci
• Gram negative enteric bacilli : E coli
• Listeria monocytogenes
b. From 2 month to 12 years
• Hemophilus influenza type B
• Pneumococci
• Meningococci

2. Viral
a. Enteroviruses (e.g. echo virus, Coxsackie) are the commonest.
b. Epstein-Barr virus, adenoviruses and mumps.

3. Tuberculous meningitis

4. Other rare causes:

a. Mycoplasma
b. Fungal infections

Acute bacterial meningitis

Source of infection
1. Hematogenous dissemination from a distant site (nasopharynx) -> choroid plexus of
the lateral ventricles -> meninges and CSF.

2. Bacterial invasion from a contiguous focus (sinusitis, otitis media, mastoiditis)

Pathophysiology
1. Early: leukocyte infiltration and activation leading to release of inflammatory mediators. So,
edema and endothelial damage and small infarctions occur.

2. Later: fibrosis can lead to obstructive hydrocephalus.

22
Clinical manifestations

A. Systemic manifestations
1. Fever, poor feeding, vomiting, lethargy, myalgia and arthralgia
2. Purpura fulminans or erythematous rash, disseminated intravascular coagulopathy and may
be shock (meningococcemia)
> Purpura in a febrile child should be assumed to be due to meningococcal sepsis.
> Meningococcal septicemia can kill children in hours. Optimal outcome requires immediate
recognition, rapid resuscitation and antibiotics.

B. Manifestations of increased intra-cranial tension

In infants
I. Bulging fontanelle and separated sutures: late signs.
In older children
1. Projectile vomiting.
2. Severe headache. Bulging
Fontanel
3. Blurring of vision (papilledema): late sign.
4. Abducent or Oculomotor nerve paralysis.

5. Hypertension with bradycardia and irregular shallow breathing (late signs)

C. Manifestations of meningeal irritation: absent in infants less than 18 months)

1. Neck pain and rigidity: passive flexion of the neck is difficult and painful.

23
2. Kernig's sign: if the hip and knee joint are flexed at 90, extension of the knee will be
limited.
3. Brudzinski sign: if the neck is flexed—> the hips and knees will be flexed too.
4. Arched back (opisthotonus): late sign

D. Manifestations of neurological deficits

1. Disturbed Conscious level: drowsiness, reduced consciousness or even coma.
2. Convulsions.
3. Focal neurological signs: paresis or paralysis, and spasticity.

Investigations
CSF examination
1. Differentiating bacterial meningitis from tuberculous and viral meningitis (table)
2. Culture and sensitivity tests are essential: negative with ( pervious intake of antibiotics or in
aseptic meningitis e.g. Viral)
3. Detection of antigens (PCR) and antibodies (ELIZA) of viral infection if viral meningitis is
suspected
4. Ziehl-Nielsen staining of the CSF if TB meningitis is suspected (may show acid-fast bacilli)

Normal Bacterial Tuberculous Viral

Aspect Clear Turbid Opalescent Usually Clear

Chemical
Protein: mg/dl 20-40 marked 1 s Normal or mild

Glucose: mg/dl 40-80 sk very low 4/ Normal

60% of blood
glucose

Cells/ mm 3 T
Lymphocytes Polymorph. lymphocytes lymphocytes
0-5 10-100,000 250-500 15-2000

Contraindications of lumbar puncture

1. Cardiopulmonary instability
2. Coagulopathy or thrombocytopenia
3. Coma with (GCS less than 9)
4. Marked increased intracranial tension
5. Infections at the site of lumbar puncture.

24
Other investigations
1. CBC: marked leukocytosis with bandemia
2. Blood culture
3. Kidney functions test and electrolytes
4. Coagulation screen if DIC is suspected
5. If TB is suspected: chest X ray, tuberculin rest.
6. CT with contrast to detect meningeal enhancement
7. MRI brain for better visualization of cerebral infarcts.

Complications: Common in pneumococcal infection than meningococcal infection

A. Early complications (occur during the course of illness)

1. C.N.S
a. Subdural effusion: (confirmed by CT)
b. Convulsions focal or generalized.
c. Cerebral abscess: there is deterioration of clinical condition with the appearance of
signs of a space-occupying lesion. It is confirmed by CT scan.

2. Others
a. Disseminated intravascular coagulopathy.
b. Shock due to acute adrenal insufficiency.
c. Inappropriate antidiuretic hormone release resulting in hyponatremia.
d. Spread of infection and septicemia

B. Late complications (occur after recovery and require follow up): CNS
complications
1. Hydrocephalus due to inflammatory obstruction of CSF pathways.
2. Subdural empyema that increases the intracranial tension.
3. Epilepsy due to focal infarctions and adhesions with underlying cortical irritation.
4. Mental retardation, cerebral palsy and learning deficits.
5. Deafness: damage of the 8th cranial nerve and cochlear hair cells.

Prevention
1. Vaccination

25
 a. Infants in the first year of life: HIB vaccine (against Hemophilus influenza) and
pneumococcal conjugate vaccines
b. Children: at 2-3 years of age.-Meningococcal polysaccharide vaccine
2. Chemoprophylaxis
Rifampicin Rifampicin in meningococcal nasopharyngeal carriers and household contact

Treatment

■ Supportive treatment
a. I.V fluid if meningitis is complicated by shock (otherwise fluid is restricted to minimize
cerebral edema: only 75% of maintenance is given)
b. Anticonvulsants: diazepam and phenobarbitone.
c. Assisted ventilation if respiratory failure occurs.
d. Subdural taps to evacuate extensive subdural effusions

2. Specific treatment
a. Antibiotics: IV for at least 10-14 days (in neonates 3 weeks).
Initial antibiotics are based on the patent's age, and then modified according to the
result of culture and sensitivity tests.
• Neonates and infants below 2 months:
Third generation cephalosporins e.g. Cefotaxime 200 mg kg/day plus ampicillin
lOOmg/kg/day.
■ Infants and children above 2 months:-
Third generation cephalosporin e.g. Ceftotaxime 200mg/kg/day.
b. Dexamethasone) in H influenza infection to decrease incidence of gliosis and hearing
loss

3. Follow up to detect late complications e.g. Epilepsy and mental retardation

By periodic monitoring of neurological and developmental status for (at least 2 years)

TB meningitis
Clinical picture:
1. Severe systemic manifestations more than bacterial
2. TB meningitis should be considered in any case of aseptic meningitis.
Investigations; see before
Treatment
Anti TB drugs should be started when diagnosis is suspected (a combination of 4 drugs)

Viral meningitis: 2/3 of cases of meningitis

Clinical picture
1. More abrupt but milder than acute bacterial meningitis.
2. Consciousness is usually not affected and most cases recover well.
Investigations: see before
Treatment: supportive

26
 Encephalitis

Definition
Diffuse viral infection of brain parenchyma

Etiology

1. Herpes simplex type I and type II: It causes encephalitis year-round, (sporadic) (the most
common)
2. Enteroviruses ( Echo and Coxsackie): Cause encephalitis outbreaks during summer
3. Epstein Barr virus.
4. Arboviruses: outbreaks during the summer (mosquitoes born) Examples: California
encephalitis virus.
5. Viruses associated with childhood illness; Measles, rubella, Chicken pox, and Mumps
6. Other rare causes of encephalitis: Rabies, CMV, and HIV viruses

Clinical picture
It is not possible to clinically differentiate encephalitis from meningitis, and treatment
for both should be started once diagnosis is suspected
1. Manifestations of Viremia (early features): fever, nausea, and upper respiratory symptoms.
2. Manifestations of increased intracranial tension less severe than meningitis:
3. Manifestations due to neurological deficits
• Disturbed level of Consciousness, irritability, abnormal movements, confusion up to deep coma
■ Convulsions
■ Paralysis or paresis and spasticity are common..
4. Manifestations of complications (post encephalitic sequelae) may develop later on:-
■ Epilepsy due to focal adhesions with underlying cortical irritation
■ Mental retardation, cerebral palsy and learning deficits

• Auditory, visual, speech and behavior abnormalities.

Investigations
Laboratory
1. CSF examination : see table
CSF PCR, Culture and sensitivity and BACTEC may be done
2. Serological tests: to detect antiviral antibodies
Imaging

1. CT scan and MRI: They may reveal focal or generalized abnormalities

MRI: helpful in post infectious encephalitis (may show foci of demyelination). In herpes
encephalitis there is temporal lobe demyelination
2. EEG: A diffuse, bilateral slowing of background activity is the most usual finding.
In herpetic encephalitis, there might be focal lesions in temporal areas,

27
Treatment
1. Supportive: ICU management
a. Basic life support: A+B+C
b. Control of convulsions (diazepam and phenobarbitone)
c. Dehydrating measures to lower the increased intracranial tension.
a. Head elevation 30 0
in neutral position.
b. Osmolar therapy with mannitol or hypertonic saline,
c. Mechanical hyperventilation in severe cases.
2. Antiviral therapy: possible only with Herpes simplex encephalitis: Acyclovir There
is no specific therapy for other types of viral encephalitis

Brain abscess
Incidence
Most common between 4-8 years
Etiology
• Organisms: Staph aureus, streptococci and others.
• Origin:
1. Direct spread from sinusitis, dental infection, orbital cellulitis, chronic otitis media and
mastoiditis.
2. Direct spread from face, scalp, dental infection and penetrating head injuries.
3. Penetrating head injuries, meningitis and infected ventriculo-peritoneal shunt
4. Distant spread: Congenital cyanotic heart diseases.
Pathology
■ Sites: frontal, parietal and temporal lobes are the most commonly affected
■ Number: single or multiple (multiple brain abscesses are common with meningitis)

Clinical picture
1. Manifestations of toxemia: fever
2. Manifestations of increased tension: Headache, vomiting
3. Focal neurological signs: - Hemiparesis, convulsions and may be coma

Investigations: CT or MRI brain which is the most reliable

1. Plain CT-> rounded hypodense lesion.
2. Contrast CT-> the abscess capsule shows ring enhancement
Treatment: combination of antibiotics for 4-6 weeks and drainage

28
 Acute Disseminated Encephalomyelitis (ADEM)

Definition
It is an inflammatory, demyelinating disorder with multifocal neurologic deficits, typically
accompanied by encephalopathy.

Epidemiology
ADEM can occur at any age but most series report a mean age between 5 and 8 yr.
Etiology
Molecular mimicry induced by infectious exposure or vaccine may trigger production of CNS
autoantigens. Many patients experience a transient febrile illness in the month prior to ADEM
onset.

1. Post infectious ADEM occurs after viral or bacterial infections such as influenza, Epstein-
Barr virus, cytomegalovirus, varicella, enterovirus, measles, mumps, and rubella, herpes
simplex, and Mycoplasma pneumoniae.

2. Post-vaccination ADEM has been reported following immunizations for rabies, smallpox,
measles, mumps, rubella, Japanese encephalitis B, pertussis, diphtheria, poliomyelitis
tetanus, and influenza.

Clinical picture
1. Initial symptoms: lethargy, fever, headache, vomiting,
2. Meningeal signs e.g. neck rigidity
3. Seizures, including status epilepticus.
4. Encephalopathy is a hallmark of ADEM, ranging from ongoing confusion to persistent
irritability to coma.
5. Focal neurologic deficits can occur and include
a. Visual loss, cranial neuropathies
b. Ataxia, motor and sensory deficits
c. Bladder/bowel dysfunction with concurrent spinal cord demyelination.

Investigations
1. CT brain may be normal or show hypodense regions.
2. Cranial MRI, the imaging study of choice: typically exhibits large,
a. Multifocal T2 lesions with variable enhancement within white and often gray matter of
the cerebral hemispheres, cerebellum, and brainstem.
b. Deep gray-matter structures (thalami, basal ganglia) are often involved.
c. Spinal cord may have abnormal T2 signal or enhancement, with or without clinical signs
of myelitis.
3. EEG: often show generalized slowing, consistent with encephalopathy

29
4. CSF analysis
■ Pleocytosis with lymphocytic or monocytic predominance.
■ CSF protein can be elevated.

Treatment:

1. High-dose intravenous steroids (methylprednisolone) 20-30 mg/kg per day for 5

days with a maximum dose of 1,000 mg per day). Followed by an oral prednisone taper over
1 month.
2. Other treatment options include intravenous immune globulin (usually 2 g/kg
administered over 2-5 days) or plasmapheresis.
3. In severe cases rituximab or cyclophosphamide has been used.

30
 Neuromuscular disorders

Anterior horn cells

1. Werdnig Hoffmann disease: genetic disease presents with severe hypotonia (floppy
infant).
2. Poliomyelitis: infectious disease presents with acute paralysis.

Peripheral nerves
1. Hereditary motor sensory neuropathies.
2. Acute post infectious polyneuropathy (Guillain Barre syndrome).
3. Bell's palsy.

Neuro muscular junction

1. Myasthenia gravis: autoimmune disease, presents with motor weakness.
2. Botulism: presents with acute paralysis.

Muscles (myopathy)
1. Muscular dystrophies: Duchenne - Becker- congenital.
2. Inflammatory myopathies: dermatomyositis.
3. Metabolic myopathy.
4. Congenital myopathy.

Posterior
root

Anterior
horn cells
Anterior
root

31
 Floppy Infant

Definition
Severe persistent hypotonia presenting at birth or in early infancy

Etiology
Central (cerebral) causes
1. Atonic cerebral palsy.
2. Cortical malformations.
Genetic causes
1. Down syndrome
2. Prader-Willi syndrome

Peripheral: Neuromuscular disorders

1. Anterior horn cells: spinal muscle atrophy: Werdnig Hoffmann disease. The most common
2. Peripheral Nerves: hereditary neuropathy
3. Neuromuscular junction: transient neonatal myasthenia.
4. Muscle diseases: congenital myopathy

Down Prader- Willi

syndrome syndrome

Clinical manifestations of hypotonia

1. Hypotonia of neck muscles-^ head lag.

32
Spinal muscle atroph
Definition
Hereditary disease characterized by progressive hypotonia and muscular weakness due to
degeneration of the anterior horn cells
Incidence: the most common cause of floppy infant
Etiology
■ Transmission : autosomal recessive (gene in chromosome N 5)
■ There is progressive degeneration of the anterior horn cells due to apoptosis.

Types of SMA
o SMA type 1( severe infantile form) (Werdnig Hoffmann)
o SMA type 2 (slowly progressive with delayed onset)
o SMA type 3(the mildest as patients are ambulatory
o SMA type 0 (fatal in the perinatal period)

Clinical picture of SMA type 1( Werdinq Hoffmann disease)

a. Intrauterine: diminished fetal movements are often noticed during pregnancy
b. At birth
a. Arthrogryposis (positional deformities of the limbs)
b. Floppy infant: see before
c. Later on
1. Motor system
o State: muscle wasting and fasciculations (worm like movement: best seen in the
tongue: characteristic clinical sign).
o Power and tone : severe weakness and severe hypotonia
2. Reflexes: absent tendon reflexes
3. Cranial nerves: bulbar paIsyWeak cough and weak cry
4. Normal mentality and normal eye movement.
5. Late respiratory paralysis -^death in late infancy from respiratory failure

Investigations
1.
Electromyography
2. Genetic Study

Treatm
ent1. Pulmonary complications(treatment of chest infection and pulmonary ventilation

2. Nasogastric feeding may be needed

3.
Physiotherapy
4. New emerging therapies are now evolving based on the genetic testing (Gene therapy)

33
 Acute paralysis

Etiology
1. Cerebral : strokes e.g. infective endocarditis
2. Spinal cord
a. Transverse myelitis
b. Spinal cord trauma as in traffic road accidents.
3. Anterior horn cells
Poliomyelitis: asymmetric ascending paralysis.
4. Peripheral nerves
a. Guillain Barre syndrome (the commonest cause): Symmetric
ascending paralysis.
b. Post diphtheritic paralysis: Symmetric descending
5. Neuromuscular: Botulism: symmetric descending paralysis

Acute post infectious polyneuropathy: Gillian Barre syndrome

Definition
Acute post-infectious polyneuritis with demyelination of the peripheral nerves characterized
by acute loss of motor functions within hours or few days due to the
formation of antibody attaching itself to protein components of myelin
Incidence
It is the most common cause of acute paralysis in children
Etiology
c. It follows bacterial infections e.g. Campylobacter jejuni or viral infections e.g.
Cytomegalovirus or post vaccination
* Manifestations are due to post infectious demyelination.

Nerve axon

34
Clinical picture
1. History: preceding infection or vaccination as respiratory or GIT infection few weeks before
the onset of paralysis.
2. Neurological examination
a. Motor: acute paralysis which is:
o Ascending
• Begins in the lower limbs and progressively ascends within hours or days to
involve the trunk and upper limbs.
• Respiratory muscles affection leads to paradoxical breathing (seesaw abdominal
movements) -»respiratory failure
o Symmetrical
o Associated with hypotonia : (Lower motor neuron disease)
b. Reflexes hyporeflexia or areflexia
c. Sensations: paresthesia in the distal part of the limb (less prominent than paresis
d. Autonomic: changes in blood pressure and heart rate so cardiovascular monitoring is
important
e. Cranial nerves: facial and bulbar paralysis may occur -> aspiration
3. Recovery
a. The paralysis usually remains stationary for few weeks followed by gradual complete
recovery over few or several weeks.
b. In some patients paralysis may persist for several months with incomplete recovery

Investigations
* Diagnosis is mainly clinical
1. CSF analysis (2 weeks after the onset of paralysis)
Increased protein but with normal cell count and glucose (Cytoalbuminous dissociation)
2. EMG: Decreased nerve conduction velocity ( diagnostic)

Increased protein Normal cells

Treatment
1. ICU and mechanical ventilation for cases with respiratory muscles paralysis or
bulbar paralysis (lifesaving).
2. IV gamma globulin in all patients for 5 successive days. The best choice
3. Plasmapharesis.
4. Physiotherapy should start from the second week of illness.

35
Poliomyelitis

Incidence
In Egypt, it is almost eradicated with the compulsory vaccination

Etiology
1. Acute viral infection of the anterior horn cells.
2. Transmission: is oral and droplet.
3. Man is the only reservoir.

Immunity
1. Trans-placental passive immunity persists for about 6 months.
2. Active immunity after vaccination or infection is lifelong

Clinical types
1. Unapparent infection (90-95% of cases)
2. Abortive poliomyelitis (5-10%)
3. Non paralytic
4. Paralytic (1-2 %)
5. Encephalitic poliomyelitis

Diagnosis of paralytic poliomyelitis

1. Acute paralysis
a. Type
o Lower motor neuron lesion (hypotonia, hyporeflexia).
o Pure motor no sensory affection as the site of destruction is the anterior
horn cells or cranial nerve nuclei (Polio = gray matter. Myelitis =spinal cord
inflammation).
b.
Distribution
o Unilateral and if bilateral, it is asymmetrical. Lower limbs (One limb is more affected )
and may extend to the abdominal muscles, trunk and neck
o In some patients, bulbar and respiratory paralysis may occur.

2. Gradual incomplete recovery: paralysis remains stationary for several weeks after which
gradual incomplete recovery.

Prevention: polio vaccine (see vaccination)

Treatment
1. Acute stage (first 2 weeks): isolation and treatment of bulbar and respiratory affection.
2. Restoration stage (2 weeks to 6 months): physiotherapy.
3. Residual stage (after 6 months): orthopedic correction of contractures.

36
 Progressive Motor Weakness

Etiology
1. Cerebral causes
o Brain tumors and cysts.
o Degenerative brain diseases.
2. Spinal cord causes
o Compression paraplegia (spinal cord tumors, Pott's disease), o
Degenerative diseases of the spinal cord.
3. Peripheral nerves
Hereditary motor sensory neuropathy
4. Neuromuscular junction: Myasthenia gravis
5. Muscular causes
Muscular dystrophies (Duchenne muscular dystrophy is the Most
common cause of progressive muscle weakness)

Clinical evaluation
1. Differentiate between upper and lower motor neuron lesions
a. Upper motor neuron lesions: hypertonia and hyperreflexia
b. Lower motor neuron lesions: hypotonia and hyporeflexia

2. Diagnosis of the cause

o Cerebral causes: increased intracranial tension, convulsions or mental affection are
usually present.
o Spinal cord lesions: lower limbs only are usually affected; other manifestations as urinary
incontinence of urine are usually present.
o In muscular dystrophy progression is very slow over years and in Duchenne type there is
pseudo hypertrophy of calf muscles is present.

Investigations
The investigations depend mainly on the clinical suspicion:
1. CT and MRI in suspected brain or spinal cord lesion
2. Serum CPK, electromyography and muscle biopsy with suspected muscular disease

37
Duchenne Muscular Dystroph
Incidence
The most common and most serious muscular dystrophy

Etiology
X linked recessive disorder (mutation in Dystrophin gene in Xp21):

Pathogenesis
1. Defect in production of protein called dystrophin which maintains the integrity of the
muscle cell wall
2. An influx of calcium ions, and excess of free radicals
3. Irreversible destruction of the skeletal muscles

Pathology
1. Atrophy of muscles (mainly proximal) e.g. pectoralis major and brachioradialis
2. Some muscles show pseudo hypertrophy (replacement of muscle fibers by fat and
fibrous tissue) e.g. calf and deltoid muscle.

Clinical picture: males are only affected

History
The onset is usually during the first 5 years or before
1. The 1st presentation is clumsy child with slow movement.
2. Difficulty in getting upstairs and in getting up from sitting position, of gradual onset
and slowly progressive course up to difficulty in walking.
3. Family history may be positive from the mother
Examination

A. Neurological examination

1. State: pseudo hypertrophy of calf muscles (early and constant sign) followed by
muscle of the forearm.
2. Power and tone
a. Weakness and hypotonia of muscles of pelvic girdle ->
o Waddling gait
o Positive Gower sign: The boy climbs up his legs to rise From
the sitting position
b. Weakness and hypotonia of shoulder girdle muscles-^
o Inability to comb the hair
o Inability to raise the arm above the head
c. Weakness and hypotonia of trunk muscles ->
o Winging of the scapula
o Increased lumbar lordosis
o Protruded abdomen.

38
B. Other systems
1. Heart: cardiomyopathy^ cardiomegaly
2. Skeletal deformities: as pes cavus or Scoliosis (common complication)
3. Mild mental affection

Gower sign

Scoliosis Wining of the

Investigations Scapula

1. Serum CPK (creatine kinase) .Marked elevation even at birth (can be used as
screening test).
2. Electromyography
3. DNA studies: deletion on Dystrophin gene
4. Muscle biopsy: diagnostic (absent Dystrophin).

Treatment
1. Nutritional support and physiotherapy.
2. Night splints to prevent contractures - Scoliosis is managed with a truncal brace
3. Treatment of chest infections and respiratory aids CPAP.
4. Corticosteroids: to preserve mobility and prevent scoliosis (its action may be inhibition of
muscle proteolysis, anti-inflammatory effect.).
5. Gene therapy is now available^

Prognosis
o Unable to walk by the age of 10 years
o Die between 15-25 years with respiratory infections.
Cause of Death: respiratory infection, respiratory failure and heart failure

Differential diagnosis (other muscular dystrophies)

1. Beker dystrophy (x linked recessive) delayed onset, slower course.
2. Limb girdle dystrophy. Autosomal recessive (The pelvic girdle muscles are more affected
than the shoulder girdle muscles.
3. Metabolic myopathies e.g. glycogen storage disease e.g. lipid myopathy and
mitochondrial myopathy

39
 Neurodevelopmental and Behavioral Disorders

Autistic Spectrum Disorder

Clinical features
Autism spectrum disorders (ASD) describe a spectrum of disorders of varying severity but with
a triad of impairments in common:
1. Impaired social interaction (with poor eye contact as an early sign)
2. Impaired verbal and non-verbal communication and impairment in imagination
3. Restricted, repetitive or stereotyped behavior

It may be accompanied with intellectual disability, but some children express unusual abilities
in some learning domains (i.e. math, etc). It presents in early childhood.

Risk factors:
No single etiological factor in the development of ASD, but there are a number of factors which are
known to be associated with an increased risk of ASD. These are:
1. A family history of autism.
2. Preterm birth.
3. Parental mental health disorders (particularly schizophrenia and related disorders).
4. Maternal use of sodium valproate in pregnancy.
5. Neonatal encephalopathy or epileptic encephalopathy, including infantile spasms.
6. Chromosomal disorders such as Down's syndrome.
7. Other genetic disorders such as neurofibromatosis, tuberous sclerosis, fragile X syndrome.

N.B. No link has been proven between increased risk for autistic spectrum disorders and
vaccinations (such as MMR vaccine).

Management:
It is based upon clinical manifestations of the disorder and may include:
1. Interventions for core features of ASD
2. Interventions for mental health and medical morbidities
3. Interventions for behavioral difficulties
4. Medications may be effectively used to treat specific co-morbidities, such as ADHD
5. Anti-psychotic, anti-depressant and anti-epileptic medications should not be used in the core
management of autism spectrum disorder, nor should exclusion diets be recommended (e.g.
gluten free, casein free).

40
Attention Deficit Hyperactivity Disorder (ADHD)

Definition
ADHD is a disorder consists of hyperactivity, impulsivity and inattention

Incidence
o Depending on the diagnostic criteria used, the prevalence amongst school-age children ranges
from 1-2% to 3-9%
o 3 times more common in boys than in girls

Clinical Features
Symptoms have to develop before the age of 7 years, and persist for 6 months at least, in two or
more settings (e.g., home and school), with these symptoms resulting in impairment in major life
activities (family, school, peers, community) and not being easily attributable to other mental
disorders. Symptoms include:

A. Inattention: is signaled by six or more of the following symptoms that have persisted
for at least 6 months:

1. Often fails to give close attention to details or makes careless mistakes in school, work, or
other activities
2. Often has difficulty sustaining attention in tasks or play activities
3. Often does not seem to listen when spoken to directly
4. Often does not follow through on instructions, and fails to finish schoolwork, tasks, or duties
in the workplace (not due to oppositional behavior or failure to understand instructions)
5. Often has difficulty organizing tasks and activities
6. Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental
effort(such as schoolwork or homework)
7. Often loses things necessary for tasks or activities(e.g., toys, school assignments, pencils,
books, or tools)
8. Is often easily distracted by unnecessary stimuli
9. Is often forgetful in daily activities

B. Hyperactive-impulsive behavior: developmentally inappropriate levels of six or more

of the following symptoms must likewise be present for 6 months:

1. Often fidgets with hands or feet or sit restlessly in seat.

41
 2. Often leaves seat in classroom or in other situations in which remaining seated is
expected
3. Often runs about or climbs excessively in situations in which it is inappropriate (in
adolescents or adults, this may be limited to subjective feelings of restlessness)
4. Often has difficulty playing or engaging in leisure activities quietly
5. Is often "on the go" or often acts as if "driven by a motor"
6. Often talks excessively
7. Often blurts out answers before the questions have been completed
8. Often has difficulty awaiting turn
9. Often interrupts or intrudes on others (e.g. Into conversations or games)

Risk factors:
Although the exact etiology of ADHD is not completely understood, there are a number
of risk factors which seem to be associated with the disorder:
1. Preterm birth or low birth weight
2. Maternal illicit drug use, alcohol use or smoking during pregnancy
3. Close family history of ADHD
4. Exposure to some environmental toxins, particularly lead
5. High levels of family conflict
6. Syndromic associations, e.g. neurofibromatosis type 1

Management:
1. In all children with ADHD, behavioral management is an essential part of management,
through parenting support groups and parenting courses.
2. The child may be offered extra support in school, cognitive behavior therapy (CBT) or social
skills training.
3. In children with ADHD causing severe impairment to daily activities and learning, medical
treatment (stimulants) may be started. The three main drugs of choice for ADHD are
Methylphenidate, Atomoxetine and Dexamphetamine.

42
 Evaluation of a child with cardiac disease
____

A) History:
• Pulmonary venous congestion
■ Systemic venous congestion
• Cyanosis, cyanotic spells and squatting
■ Low cardiac output
• Palpitation
■ Chest pain: Most children complaining of chest pain do not have a cardiac condition
• Rheumatic fever: recurrent tonsillitis, migratory arthritis or abnormal movement
• Infective endocarditis: fever in cardiac patients should be taken seriously

B) Examination:
■ General appearance: RD, dyspnea, retraction, sweat on the forehead, orthopnea
• Anthropometric measurements: long standing HF will affect weight not height
■ Chromosomal syndromes:
■ Central cyanosis
• Pallor: it may be seen in infants with VC from severe CHF or shock
■ Jaundice: may be seen in severe systemic venous congestion
• Heart rate; tachycardia is the first sign of HF
• Respiratory rate
■ Blood pressure in the 4 limbs (to rule out coarctation)
• Radio-femoral pulse delay
■ Extremities: Perfusion, edema, cyanosis and clubbing
• Congested neck veins: > 2 cm above the clavicle (patient lies in 45 degree)
• Prominent arterial pulsation "Corrigan sign": Peripheral signs of AR
■ Carotid thrill: AS.
• Local cardiac examination:

C) Investigations
1. CXR for assessment of:
■ Heart: Cardiomegaly, chamber enlargement and special configuration (e.g., TGA)
■ Chest: Pulmonary blood flow and chest infection
2. ECG for detection of: Special EC HO
• Chamber enlargement '"Transesophageal ECHO (TEE)
■Arrhythmias Fetal ECHO (17-19 wks)
3. Echocardiography and Doppler for study of:
• Anatomical defects: Valvular lesions, septal defects and pericardial effusion
■ Vegetations

4. Cardiac Catheterization and

angiography

Echocardiograp Cardiac
hy Catheterization
43
 Congenital Heart diseases

- 8:1000 of full term live births

- VSD is the most common (25-30%)
- 10-15% have complex lesions (more than 1 cardiac anomaly)
- 10-15% also have a non-cardiac abnormality
- CHD is the commonest structural malformation

Etiology
1. Chromosomal:
■ Down syndrome: Endocardial cushion defects, VSD, ASD, TGA
■ Turner syndrome: coarctation of the aorta or aortic stenosis.
■ Patau syndrome
■ Edward syndrome

2. Environmental factors:
■ Congenital infection (Rubella): PDA
■ Maternal diseases: Diabetes (CHD), SLE (complete heart block)
■ Maternal drugs: Wafarin (pulmonary stenosis), alcohol (VSD)
■ Maternal irradiation

3. Multifactorial polygenic): Interaction between genetic and environmental factors

Classification

A) Congenital Acyanotic heart diseases (80%)

Left to Right shunt Obstructive lesions

Pulmonary Blood Flow Normal PBF
Ventricular septal defect (30%) * Aortic stenosis (5%)
Atrial septal defect (5-10%) ■ Pulmonary stenosis (7%)
* Coractation of aorta (5%)
Patent Ductus Arteriosus
(5-10%) Atrioventricular canal
(2%)

B) Congenital cyanotic heart diseases ( 20%)

Pulmonary Blood Flow f Pulmonary Blood Flow

■ Fallot tetralogy (5%) • Transposition of great arteries TGA
■ Fallot-like conditions (e.g., PS + (5%)
VSD) ■ Hypoplastic left heart syndrome
■ Tricuspid atresia ■ Single ventricle
■ Pulmonary atresia ■ Truncus arteriosus

44
Clinical picture:
1. Antenatal cardiac ultrasound diagnosis (at 18-20 weeks of gestation)
2. Detection of heart murmur
3. Cyanosis
4. Heart failure

Complications of congenital heart disease in general:

A) Complications of congenital acyanotic heart diseases

■ Chest infections
• Heart failure
■ Infective endocarditis
■ Pulmonary hypertension (PH)
■ Reversal of shunt (Eisenmenger syndrome): due to pulmonary hypertension with
appearance of cyanosis in previously acyanotic child
■ Failure to thrive (FTT)
• Obstructive lesions: syncope, sudden death, heart failure

B) Complications of congenital cyanotic heart diseases

■ Thrombosis (Polycythemia)
■ Brain abscess (Rt to Lt shunt bypass of lung filter)
■ Infective endocarditis
■ Failure to thrive

45
 Ventricular septal defect

Anatomical Defect
1. Defect in the interventricular septum:
■ Membranous or perimembraneous (80%)
■ Muscular (20%): Single or multiple (Multiple muscular may be named Swiss cheese
VSD)
2. VSD may be isolated or associated with other CHD

Hemodynamics
■ Blood is shunted from the LV to RV during the systole (The amount of shunt depends
on the size of the defect)
■ No shunt occurs during diastole
• Lung plethora: increased pulmonary blood flow
■ Biventricular enlargement

Small VSD (< 3 mm)

A) History: Asymptomatic
B) Examination
a. General: Normal
b. Cardiac: Pansystolic murmur (Describe as below)
C) Investigations:
- CXR, ECG: Normal
- ECHO: Diagnostic
D) Treatment
- Reassurance (Spontaneous closure is common)
- Prophylaxis against infective endocarditis

Large VSD

A) History

46
 1. Onset: second week of life
2. Feeding difficulties, failure to thrive (FTT) and excessive sweating in infants
3. Dyspnea, exercise intolerance in older children
4. Recurrent chest infections (Cough...)

B) Examination
a. General
• FTT (Heart failure)
■ Recurrent chest infections

b. Cardiac
■ Inspection and Palpation
o Biventricular enlargement mainly the left ventricle (active precordium) o
Systolic thrill over the Lt parasternal area
■ Auscultation
o Accentuated S2 (Pulmonary hypertension)
o Murmur
- Timing: Pansystolic
- Character: Harsh
- Maximum intensity: Lt parasternal area (3rd and 4 th spaces)
- Selective propagation: All over the precordium

Complications
1. Heart failure
2. Recurrent chest infections
3. Infective endocarditis
4. Failure to thrive
5. Pulmonary hypertension and Eisenmenger syndrome:
- High pulmonary flow leads to pulmonary vasoconstriction

- Reversal of the shunt across the VSD due to pulmonary hypertension with
appearance of cyanosis in previously acyanotic child
- So early intervention is essential

Investigations
1. Chest X ray
■ Heart: biventricular enlargement
■ Chest: Lung plethora
2. ECG: biventricular hypertrophy (mainly the left ventricle
3. ECHO will assess
- Position and size of the defect and blood flow across
- Pulmonary pressure
- Cardiac dilation and efficacy of contractility

47
Treatment
A) Medical
■ Infective endocarditis (Prophylaxis and treatment)
■ Proper nutrition
■ Management of HF: discuss
■ Treatment of chest infections

B) Surgical closure (Surgery or catheter)

■ Indications:
a. Large defect with failure of medical treatment
b. Infant 6-12 months old with large VSD and pulmonary hypertension

■ Surgery should be delayed in stable child with moderate VSD. "Spontaneous closure"
■ Surgery is contraindicated in patients with Eisenmenger syndrome
■ Heart-lung transplantation is the only surgical option for Eisenmenger syndrome
■ Pulmonary artery banding may be useful

Prognosis
■ 30%: close spontaneously
■ Large VSD: heart failure in 6 weeks or Eisenminger syndrome as early as 6 months

48
 Persistent ductus arteriosus

Incidence and etiology

More common in female, congenital Rubella syndrome, preterm infants

Anatomical Defect
1. Persistence of the ductus arteriosus
2. Site: Just distal to the origin of the left Subclavian artery

Hemodynamics
■ Blood is shunted from aorta to pulmonary artery during systole and diastole
■ Lung plethora: increased pulmonary blood flow
■ Lt atrial and Lt ventricular enlargement

Pulmonar
y
Remember
I

Intrauterine Function
of
I
the ductus
Shunting of blood from
PA to Aorta
Closure of the ductus
■Functional: Soon after
birth (O 2 )
•Structural: Within weeks

Small PDA: As small VSD

A) History: Asymptomatic
B) Examination
a. General: Normal
b. Cardiac: Murmur (Describe as below)
C) Investigations: as small VSD
D) Treatment
- Catheter closure
- Infective endocarditis (Prophylaxis)

Large PDA
A) History: As large VSD
B) Examination

49
 a. General
■ FTT
■ Recurrent chest infections
■ Hyperdynamic circulation: : Big pulse volume (water hammer sign)

b. Cardiac
■ Inspection and Palpation
o Lt ventricular enlargement
o Systolic thrill over the Lt infraclavicular area

■ Auscultation
o Accentuated S2 (Pulmonary hypertension)
o Murmur appears after the first week of life
- Timing: Continuous
- Character: Machinery
- Maximum intensity: Lt infraclavicular area
- Selective propagation: Pulmonary area (Lt 2 nd intercoatal space)

Complications
As VSD but cyanosis of Eisenmenger involves the lower half of the body

Investigations
1. Chest X ray
■ Heart: LV enlargement
■ Chest: Lung plethora
2. ECG (LV hypertrophy)
3. ECHO

Treatment
1. Medical closure: Indomethacin, ibuprofen or paracetamol (In preterm infants in 1st week)
2. Treatment of complications (heart failure and chest infections)
3. Surgical treatment: surgical or catheter closure (coil or occlusive device) before 1 year of
age

Occlusio
n
Coil Closure of PDA

50
 Atrial septal defect
Anatomical Defect
Defect in the interatrial septum:

1. Ostium secundum 2. Ostium primum

More common (80%) Less common
Less serious More serious
High defect (at site of fossa ovale) Defect in the lower interatrial septum
Normal mitral valve Cleft anterior leaflet (Mitral regurge)
May be part of atrioventricular septal defect
No mitral regurge

3. Sinus venosus defect: ASD near superior vena cava (SVC)

septal

defect

Sinus venosus
Hemodynamics
1. Blood is shunted from the LA to RA during the systole
2. Lung plethora: increased pulmonary blood flow
3. Rt ventricular hypertrophy

Complications
1. Heart failure ( delayed)
2. Chest infections
3. Rt Bundle branch block, atrial fibrillation

51
 Ostium secundum Ostium primum
Onset Usually in the 3 rd or 4"1 decades Infancy

£ Symptoms • Asymptomatic • Dyspnea, exercise

O • Dyspnea, exercise intolerance intolerance
+-
»
cn
X • Recurrent chest infections • Recurrent chest infections
• HF is uncommon • HF is common

Insp. and Palp. RV hypertrophy Biventricular enlargement

E
nj S2 Wide fixed splitting
X LU
No murmur due to ASD
Murmur Ejection Systolic over pulmonary area due to relative PS

-CXR RVH-Pulmonary plethora¬ Biventricular enlargement

+J
(/> prominent pulmonary artery
01
-ECG Rt axis deviation - Rt bundle
>
c -ECHO branch block
■Catheter.

T Mild cases Surgery (between 3-5

T No TTT years) to prevent Rt sided
Catheter closure
T heart failure and atrial
fibrillation

Atrioventricular Septal Defect

Incidence AVSD is the most common cardiac defect in Down syndrome Anatomical Defect:
Defect in the middle of the heart with single 5-leaflet AV valve

1. Partial AVCD 2. Complete AVC

xi ■ , Ostium primum, inlet VSD and
Ostium primum with mitral
mitral regurge and tricuspid regurge
Defect regurge
Biventricular enlargement
Ventricle

HF, pulmonary hypertension (develop early)

Cyanosis (Mixing defect) Normal heart Atroventncutar canail
(Endocardial cushion dele

Auscultation: accentuated S2 and

ejection systolic murmur on
C/P
pulmonary area

Medical: HF and chest infections

TTT
Surgical: at 3-6months of age (prevent PH that develops early)

52
 Coarctation of the aorta

Anatomical Defect
■ Localized narrowing of the aorta
■ Commonest site: Just distal to the origin of the Lt subclavian artery

Hemodynamics
■ Pressure gradient across the aorta
■ Increased BP in the upper part of the body
• Decreased BP in the lower part of the body
• Lt ventricular hypertrophy
• Development of collaterals (Subclavian, descending aorta and femoral)

Clinical picture
A) History:
• Mild: asymptomatic
■ Severe

o Headache and blurring of vision o

Heart failure in early infancy
B) Examination
a. General
■ Femoral pulse: Weak, absent or delayed (radio-femoral delay)
■ Hypertension in upper limb (Rt arm)

b. Cardiac
■ Inspection and Palpation
o Lt ventricular enlargement

■ Auscultation
o Accentuated A2
o Murmur

53
 - Timing: Systolic
- Character: Harsh
- Maximum intensity: Lt sternal border at the 3rd and 4 th intercostal spaces

- Selective propagation: Inter-scapular area

Complications
1. Heart failure
Rib notching
2. Intracranial hemorrhage
Due the development of large
3. Infective endocarditis
4. Hypertension collateral intercostal arteries
running under the ribs to
Investigations bypass the obstruction
1. CXR

■ Heart: LV enlargement
■ Chest: Rib notching (Older children, why?)
2. ECG (LV hypertrophy)
3. ECHO

4. Spiral CT or angiography: more preferred to assess exact affected area

Treatment
A) Medical (Infective endocarditis and HF)
B) Surgical
• Trans-catheter Stent insertion
■ Coarctectomy (Resection-anastomosis).
■ Balloon angioplasty can be used if restenosis (Recurrence)

Balloon angioplasty with stent implantation

54
 Aortic Stenosis Pulmonary Stenosis

Anatomical defect
Congenital pulmonary stenosis ■Valvular
Congenital aortic stenosis:
(Fusion of the cusps) ■Supravalvular
•Valvular (Fusion of the cusps) •Supravalvular
■Subvalvular
(as in William syndrome) ■Subvalvular (in
hypertrophic obstructive cardiomyopathy)

Hemodynamics
Obstruction of blood flow from RV
■ Obstruction of blood flow from LV
Pressure gradient across Pulm.valve Rt
■ Pressure gradient across aortic valve
■ Lt ventricular hypertrophy ventricular hypertrophy
A) History
A. History
-Mild: Asymptomatic
- Mild: Asymptomatic
-Severe: Low CO symptoms and
-Severe (Low CO symptoms): svncope, chest
cyanosis in severe cases
pain, dizziness, dyspnea., exercise
- Manifestations of Rt sided HF
intolerance
-Very severe: Lt sided HF in newborn B) Examination
A) Examination a.Cardiac
a. General ■ Inspection and Palpation:
■ Pulse: Small volume (Plateau) - RV hypertrophy
■ BP: low systolic BP - Systolic thrill (2 nd Lt space)
b. Cardiac
■ Inspection and Palpation: ■ Auscultation
-LV hypertrophy -4'4*' S2 (± Wide splitting) -
-Systolic thrill (2 nd
Rt space) Murmur
■ Auscultation Harsh ejection systolic
- 4/S2 (+ Paradoxical splitting) -Systolic Max. intensity: 2nd Lt space
ejection click Selective propagation:
- Murmur: Harsh ejection systolic Max. Infraclavicular area
intensity: 2 Rt space Selective
nd

propagation: neck
Complications
■HF and Infective endocarditis
■HF and Infective endocarditis (Rare)
RV hypertrophy
Investigations
Prominent pulmonary artery (post
LV hypertrophy
Prominent aorta (post stenotic) stenotic)

Treatment ■ Balloon valvuloplasty (TTT of choice)

If pressure gradient > 50 mmHg ■Balloon
■Surgical valvotomy (Dysplastic valve)
valvuloplasty ■Surgical: Valve repair or valve
replacement

55
 Tetralogy of Fallot

Anatomical Defect
1. Pulmonary stenosis (usually infundibular, may be valvular)
2. Big VSD (with misalignment)
3. Overriding aorta
4. RVH (mild)

Hemodynamics
1. Blood in the RV pass through 2 pathways:
■ Small part: Pulmonary artery (PS)-> 4,4, PBF
■ Large part: Aorta (Overriding)"^ Cyanosis
2. Mild RVH
3. No shunt across VSD as pressure is equal in both ventricles

Clinical picture
A) History
1.Cyanosis:
- Onset: Usually delayed (1-2 months) due to gradual narrowing of the
infundibulum and closure of the PDA
- May appear in the neonatal period (Severe cases)
- May be absent (Pink Fallot): symptoms appear with exercise only
2. Dyspnea Squatting
3. Hypercyanotic spell (See below) 4
4 Squatting Why? Bending of
popliteal and
B) Examination femoral arteries
a. General 4
Systemic
■ Failure to thrive
resistance
■ Central cyanosis
4
• Clubbing (1-2 years) PBF
4
44 Cyanosis

56
 b. Cardiac
■ Inspection and Palpation
o Left parasternal pulsation (RVH)
o Systolic thrill over the Lt 2 nd and 3 rd spaces
■ Auscultation
o Single S2
o Harsh ejection systolic murmur at ULSB (2nd and 3 rd spaces)

Complications Hemiplegia in
1. Thrombosis (Polycythemia) Fallot:
2. Brain abscess (Loss of lung filter) ■Thrombosis
3. Infective endocarditis (CHD) ■Brain abscess
■ Infective
4. Iron deficiency anemia endocarditis
NB: No recurrent chest infections "Lung oligemia"
HF is rare (>P4/ pulmonary blood failure)

Brain abscess

Investigations
1. CBC: 'f'f Hb and ‘t'f hematocrit (microcytosis if there is iron deficiency)
2. Chest X ray : Coeur en Sabot (= Boot-shape)

• Normal cardiothoracic ratio(size)

- Acute cardophrenic angle (RV apex
- Uplifted apex
• Exaggerated waist (Ipulmonary artery size)
■ Lung oligemia (Ipulmonary blood flow)

3. ECG: Hypertrophy of the right atrium and right ventricle

4. ECHO
5. Cardiac catheterization

57
Treatment
A) Medical
■ Hypercyanotic spells
■ Propranolol
■ Iron
■ Infective endocarditis (Prophylaxis and Rx)
■ Partial exchange transfusion (using FFP or albumin), When? If hematocrit is > 65-70%
■ Prostaglandin (PG 1): in duct dependent pulmonary circulation

B) Surgical
a. Palliative: Blalock-Taussig (anastomosis between Subclavian artery and the
ipsilateral pulmonary artery). Can be considered as "artificial PDA"
b. Total correction (at 6-9 months): Closure of VSD, infundibular resection and
pulmonary valvotomy

Blalock procedures

Hypercyanotic spell
Definition: Transient attacks of deep cyanosis and dyspnea
Etiology: Due to infundibular spasm and marked reduction in the PBF

Precipitating factors: Infection, acidosis, dehydration, hypoxia, crying and anemia

C/P: Dyspnea, deepening of cyanosis (coma and convulsions may develop if prolonged)

Cardiac Ex.: Murmur (disappears or decreases), Why? "Flow across the pulmonary
valve"
Complication: myocardial infarction, cerebrovascular accidents and death if left
untreated.
Treatment
- Positioning (knee-chest position/squatting)
- O2therapy
- IV fluid
- NaHCO 3 : to correct acidosis
- Sedation (SC Morphine)
- IV |3-Adrenergic blockers (Propranolol): to relax the infundibulum
- IV alpha agonist (increase systemic resistance)

58
 Transposition of Great Arteries

Anatomical Defect
1. Aorta arises from RV
2. Pulmonary artery arises from LV
3. Communication is a must [ASD, VSD or PDA]

Hemodynamics
■ 2 parallel circulations
■LV —► Pulmonary artery—► Lung—► LV ■RV
—► Aorta (Cyanosis)—► Body—► RV
■ ASD, VSD or PDA is essential

Clinical picture
A) History
1. Deep central cyanosis (Early)
- Onset: Within the 1 st few hours or days of life (Due to ductal closure)
- Not relieved by 100% O 2 (DD: Respiratory causes of central cyanosis)
2. Dyspnea
3. Manifestations of HF
4. Recurrent chest infections (Cough...
)

B) Examination
a. General
■ Failure to thrive (Heart failure)

■ Central cyanosis Central cyanosis

■ Clubbing (< 1 year) in survivors
b. Cardiac
■ Inspection and Palpation: Left parasternal pulsation (RVH)
■ Auscultation
o Accentuated S2

59
 o Murmurs: No murmur (if intact interventricular septum). Murmur of VSD may
be present
Complications
1. Thrombosis (Polycythemia)
2. Brain abscess (Loss of lung filter)
3. Infective endocarditis
4. HF and recurrent chest infections

Investigations
1. CBC: Hb and 'f'f hematocrit
2. CXR
■ Heart: Egg-on-side, narrow pedicle (narrow upper mediastinum)
• Chest: Lung plethora ('f'f PVMs)

3. ECG: Hypertrophy of the RV

4. ECHO

Treatment
1. Prostaglandin: maintains the patency of ductus arteriosus (immediately after birth)
2. Ballon atrial septostomy: Rashkind procedure ( urgent shunt)
3. Total correction (Within the first 2-3 week of life): Arterial switch

60
 Rheumatic fever

Definition
It is an autoimmune inflammatory disease following upper respiratory tract infection with
group A-P-hemolytic streptococci. It involves the joints, heart, CNS, skin, SC tissue

Incidence
- Age: Peak incidence = 5-15 years (All ages can be affected except infancy)
- Sex: Chorea is more common in $
- More common in developing countries (Streptococcal infection is prevalent)
- Family history may be positive
- The most common cause of acquired heart disease in children
- Status in Egypt: it is a major public health problem, reported in 5.1/1000 school children

Etiology
- Autoimmune following infection by group A p-hemolytic streptococci (sore throat or scarlet
fever)
- Latent period: 2-4 weeks (4 months in isolated rheumatic chorea)

Pathogenesis: (= Mechanism of tissue injury)

a. Cross reactivity:
- There is molecular mimicry between streptococci and tissue antigens (myosin,
vimentin)
- Antibodies formed against streptococcal antigens react with human tissue antigens
b. Genetic susceptibility:
- Several genes responsible for the autoimmune reaction have been described recently

Pathology
- Proliferative lesions: Aschoff nodules that heal by fibrosis
- Exudative lesion: Effusion that resolve without residual damage

Diagnosis: Revised Jones criteria

- The Jones criteria were first published in 1944
- In 2015, the American Heart Association introduced the most recent updated version
- However for moderate and high risk populations, like in Egypt, some modifications in
criteria were done to ensure not missing potential cases

61
 Evidence of recent Strept.
Major Criteria Minor Criteria
Infection
• Polyarthritis or ■ Recent scarlet fever
Monoarthritis or ■ Positive throat culture
Monoarthralgia
Polyarthralgia • Rapid antigen test

■ Carditis Fever > 38 C° • Antistreptolcoccal antibodies High

(clinical or subclinical) titre of
• Chorea Prolonged PR interval o Antistreptolysin 0 titer (ASOT)
Unless carditis is a major o Antistreptokinase
criterion
■ Erythema marginatum Acute phase reactants: o Antihyaluronidase
■ ESR > 30mm/hr o Anti-DNase
■ CRP > 3 mg/dL
■ Subcutaneous nodules

i ’Arthralgia: Joint pain

•Arthritis: Joint tenderness and painful limitation of movement ± redness, hotness
' and swelling

Interpretation of Jones Criteria

• Diagnosis of rheumatic fever depends on:

o Two major or One major and Two minor criteria AND
o Evidence of recent streptococcal infection

• Diagnosis of recurrent rheumatic fever depends on: As before or 3 minor criteria

• Diagnosis based on 2 major criteria is stronger than that based on 1 major and 2 minors
• Arthralgia should Not be considered as a minor criterion in patients with arthritis
• Prolonged PR interval should Not be considered as a minor criterion in patients with carditis
• Elevated ESR, elevated CRP and Leukocytosis are all considered as one minor criterion
• Subclinical carditis: significant cardiac affection detected by echocardiography with
absence of any murmur. Recently considered as a major criterion
• Evidence of recent streptococcal infection is required for all cases except rheumatic chorea
• Normal value for each streptococcal serological test is variable and depends upon the age of
the patient, geographical locale and the season of the year.
• In Egypt, an ASOT level >250-400 lU/mL is taken as positive
• In populations like Egypt, with endemic skin or upper respiratory group A beta hemolytic
streptococcal infections, a negative test helps to exclude, but a positive

62
 test doesn't necessarily indicate a recent infection (antibody titer may remain elevated for
months after infection)
• Probable rheumatic fever either one major or one minor manifestation OR with absence
of streptococcal serology results but in which acute rheumatic fever is the most likely
diagnosis .

1. Polyarthritis: 70 % of cases
• Polyarticular
• Large joints: Knees, ankles, wrists, elbows
• Arthritis: Pain, redness, hotness, tenderness, swelling with limitation of movements
• Migratory or fleeting (from joint to the other) and asymmetrical
• Leaves the joint completely free Monoarthritis and polyarthralgia are
• Spontaneous resolution (even without III) recently considered major criteria in high
, risk population
• Dramatic response to salicylates

2. Carditis (50% of cases)

• It is the most serious

• May be late-onset (Delayed)
• It is pancarditis (Endocarditis is the most consistent)
a. Endocarditis (valvulitis)
■ Lt sided valves are affected more Rt sided valves
■ Mitral is affected more than aortic valve
o Acute stage
-Carey-Coombs murmur: Mid-diastolic due MS (edema of the cusps)
- Mitral regurge: Damage of the cusps (Describe MR murmur?)

o Chronic stage (Fibrosis)

- Incompetence (Regurgitation): mitral regurge is the most common lesion
-Stenosis: mitral stenosis in prolonged or recurrent disease
-Double lesion

b. Myocarditis
■ Tachycardia (Disproportionate to the degree of fever)
■ Muffled heart sounds Normally
■ Cardiomegaly HR n by 10-15/min for each 1°C
H in temperature
■ Heart failure (Gallop on auscultation)

c. Pericarditis (rare): Stitching chest pain, pericardial rub and pericardial

effusion

63
 Mitral stenosis Mitral regurgitation Aortic regurgitation
Diastole Systole Diastole

3. Chorea (15% of cases)

• It is the most common cause of chorea in children ($ > c?)
• It the only neurological manifestation of rheumatic fever
• Rheumatic chorea can be the only manifestation of RF (Latent period = Months)
• It lasts for (4-18) months but is usually a self-limited condition
• The onset of chorea often calls attention to subclinical carditis. Therefore,
echocardiography is essential for all patients with chorea even in the absence of murmurs
• Manifestations:
a. Choreic movements
It is Involuntary, static, irregular, sudden, jerky, semi-purposeful movements
involving mainly the face, trunk and limbs, aggravated by emotional stress,
decreased by rest
b. Useful clinical signs
■ Darting tongue: The tongue cannot be protruded for longer than few seconds
■ Speech abnormalities (dysarthria)
■ Milk-maid grip: Inability to maintain hand grip with rhythmic squeezing
■ Boat-shaped hands: flexion at the wrist + hyperextension at the fingers
■ Pendular knee reflex
c. Emotional lability: The patient laughs or cries without a cause

4. Erythema marginatum (5% of cases)

• Site: Trunk and proximal parts of the limbs
• Shape: Erythematous non pruritic macules [Sharp
progressive margin and central fading]
• Recurrent and evanescent

be. nodules

5. Subcutaneous nodules (2-10% of cases)

• Site: Over bony prominences (Elbows, knees...)
• Shape: Painless, rounded, hard, small nodules (0.5-2 cm)
• The skin over them is not inflamed so they can easily be missed
• Indicates severe carditis

64
Differential diagnosis
1. Arthritis (see rheumatology)
2. Carditis
• CHD • Myocarditis
• Innocent murmurs • SLE
3. Chorea: Other causes of chorea: Wilson, Huntington chorea, drugs

Investigations
1. Acute phase reactants
■ CBC: Leukocytosis
■ Elevated ESR and CRP
2. Evidence of recent Streptococcal infection: see diagram
3. Cardiac assessment
■ CXR: Cardiomegaly
■ ECG: Tachycardia and prolonged PR interval
■ Echocardiography: assesses chamber enlargement, valve affection, and cardiac
contractility and detects pericardial effusion.

Complications
1. Early: Heart failure, arrhythmias
2. Late: Rheumatic heart disease, rheumatic activity (Recurrence), Infective endocarditis

Prevention
1. Primary prevention
■ Prevention of Streptococcal infection: Good housing and adequate ventilation
• Tonsillectomy for frequent recurrence
■ Proper Rx of Streptococcal throat infection
o IM Benzathine penicillin 1.200.000 IU once (Sensitivity skin test is essential) is the best
treatment
o Alternatively oral Penicillin V 15 mg/kg/day : for 10 days or oral amoxicillin 50 mg/kg/
day for 10 days
o Oral erythromycin (20 mg/Kg/day twice daily for 10 days): in patients allergic to
penicillin
■ Primary prevention is difficult because :-
o 30% of streptococcal pharyngitis are subclinical
o 30% of patients pass to RHD after subclinical carditis.

2. Secondary prevention (Prevention of recurrence of rheumatic fever)

Indicted in all patients with documented history of rheumatic fever or isolated chorea
Drug used
a. Benzathine penicillin

65
 ■ IM: every 2-3 weeks (sensitivity skin test...)
■ Dose: 1.200,000 IU for weight > 20 Kg and 600.000 IU for weight less than 20 Kg
■ Duration: 10 years after the last attack or till the age of 21 years whichever longer then
reassess:
□ No RHD: stop prophylaxis
□ RHD: continue till the of 40 years or longer
b. Oral penicillin 250 mg twice daily
c. Penicillin sensitive patients: erythromycin 250 mg twice daily
d. Oral sulphadiazine 0.5 gram once daily.

Treatment of acute rheumatic fever

A) Antibiotics
- IM Benzathine penicillin: 600.000-1.200.000 IU (Sensitivity skin test is essential)
- Given to eradicate streptococci and serves as the 1st dose of penicillin prophylaxis

B) Supportive Management
a. Diet:
■ Salt restriction in cases of heart failure
■ Fluid restriction in cases of severe heart failure
b. Rest: For patients with arthritis, carditis or heart failure

C) Specific Management
a. Arthritis
■ Salicylates 100 mg/Kg/day, 4 times / day for 2 weeks followed by
75 mg/Kg/day, 3 times/ day for 2-3 weeks
b. Carditis
■ Prednisone: 2 mg/Kg/day 4 times daily for 2 weeks with gradual tapering (Over 4
weeks)
■ Salicylates: 75 mg/Kg/day 3 times daily started with steroid tapering and
continued for 6 weeks
c. Chorea:
■ Phenobarbitone: 15 mg/Kg/day
■ Haloperidol: 0.5- 2 mg/Kg/day
■ Carbamazepine or valproic acid can be considered in severe cases

D) Treatment of complications
a. Heart failure: see later
b. Rheumatic heart disease:
■ Medical: rheumatic activity and infective endocarditis
■ Surgical: Valve repair or replacement

66
 Infective Endocarditis

Definition
Microbial infection of the endothelial surface of the heart that needs a high degree of
suspicion to make an early diagnosis

Etiology
A) Organisms
• Streptococcus viridans (most common) Staph, aureus is the most common
• Staphylococcus aureus organism affecting normal heart
■ Others: Gram -Ve bacteria (Enterococci), fungi..
. ■ HACEK: Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and
Kingel la
B) High risk
■ RHD: Lt sided valves > Rt sided valves, Regurgitation > Stenosis
■ CHD: Fallot tetralogy, TGA, VSD, PDA, Coarctation (Not ASD secundum)
■ Prosthetic valve, previous infective endocarditis, surgical shunts, residual defect

■ Intravenous drug use

■ History of previous endocarditis and cardiac transplantation
C. Predisposing factorsJRoute)
■ Dental procedures
■ Adenotonsillectomy
■ Non-sterile instrumentation of GIT or GU systems, ventriculoatrial shunt...
■ Central venous catheters

■ Intravenous drug
use

Pathophysiology
- Turbulence of blood flow across stenotic or incompetent valves damages the
endothelium
- Platelets and fibrin adhesion forming thrombi
- Circulating bacteria adhere and grow in these thrombi forming vegetations.
- Valve destruction
- Embolization of emboli to any organ in the body
- Septic embolic phenomena: osteomyelitis, meningitis, and glomerulonephritis
- Immunologic response with deposition of circulating immune complexes on various
endothelial surfaces leading to vasculitis and rash

67
Clinical picture: 75 % of cases occur in patients with preexisting cardiac disease

A) General manifestations
1. Fever, headache, anorexia, malaise
2. Pallor and loss of weight
3. Eye: Subconjunctival hemorrhage, retinal infarction
4. CNS: Embolic hemiplegia, ICH
5. Hands
■ Clubbing (Pale or toxic clubbing)
■ Osler's nodules: Pulps of fingers
■ Splinter hemorrhages: Under the nails
• Janeway lesions: painless hemorrhagic lesion with necrotic center on the palms
and soles
■ Pulse: may be absent (Embolization)
6. Splenomegaly (70% of cases)
7. Hematuria
8. Arthritis/arthralgia

B) Cardiac manifestations
1. Feature of the underlying cardiac disease
2. Appearance of a new murmur (Sea-gull murmur = rupture chorda tendinae)
3. Change in the character of an already present murmur
4. Heart failure due to valve damage

Investigations
A) Laboratory
■ Blood culture (Repeated 3 times after proper skin decontamination)
■ CBC, ESR, CRP
B) Imaging

68
 ■ CXR, ECG
■ ECHO (Vegetations)
■ Transesophageal echocardiography may be required in case of prosthetic valves

Duke Criteria for diagnosis of Infective endocarditis

Major Criteria Minor Criteria

Positive blood culture fulfilling the Predisposing factors

following criteria: Single Positive blood culture
■ Typical organism including strept,
Fever > 38°C
staph or HACEK group
Positive blood culture for atypical organisms
• 2 positive cultures of 3 cultures drawn
>12 hours apart for other organisms
Vascular Embolic manifestations
consistent with IE • Splenic infarctions
• Cerebral infarction or hemorrhage.
■ Renal infarction
■ Necrotic skin or gangrene
■ Retinal infarction
■ Conjunctival hemorrhage
• Janeway lesions
Evidence of endocarditis on ECHO: Immune complex deposition:
■ New vegetations or abscess ■ Glomerulonephritis
■ New valve regurge or variation ■ Roth spots (retinal hemorrhage with pale center)
in the degree of regurge
■ Splinter hemorrhage (linear hemorrhage under nails)
■ Osler nodules (on pulps of fingers or toes)
• Petechiae

Interpretation of Duke Criteria

Diagnosis is established with:

■ TWO major or
■ ONE major + THREE minor or
■ FIVE minor

Prevention
1. Proper oral hygiene
2. Oral, respiratory or dental procedures:
■ Oral or IV Amoxicillin single dose 50 mg/Kg; 1 hour before procedure
■ In allergic patients: Azithromycin (15 mg/Kg), Clindamycin (20 mg/Kg) oral

69
3. GIT (except esophageal) or genitourinary procedures:
■ IV ampicillin (50 mg/Kg) and IV gentamycin (1.5 mg/Kg): 30 minutes before procedure
■ In allergic patients: azithromycin (15 mg/Kg) or clindamycin (20 mg/Kg) and
gentamycin
• 6 hours after procedure: oral amoxicillin (25 mg/Kg)

Treatment
1. Prolonged parenteral therapy according to culture and sensitivity to kill all
bacteria in the vegetations

A. Empirical therapy till culture results

1. Anti-staphylococcal penicillin (methicillin) + Aminoglycoside (gentamycin)
2. Suspected methicillin resistant S.aureus: Vancomycin + gentamycin
B. According to culture
• Streptococcus viridans: Penicillin G or ampicillin or ceftriaxone for 4 weeks and
gentamycin for 2 weeks
■ Staph.aureus: vancomycin for 6 weeks AND gentamycin for 5 days.
• Enterococci: penicillin or ampicillin for 4-6 weeks AND gentamicin for 2 weeks.
■ HACEK: ceftriaxone alone or ampicillin + gentamycin for 4 weeks
■ Vancomycin if penicillin or ceftriaxone are not tolerated
■ Amphotericin B for fungal infection.
■ Patients with prosthetic valves should be treated for 6 weeks according to culture

2. Surgical care
It carries a high mortality, indicated in certain situations as
■ Progressive cardiac failure
■ Worsening valve obstruction or regurge
■ Periventricular abscess
■ Fungal infections and failed response to medical treatment as with large vegetations

Prognosis
Overall recovery rate 80-85%

70
Innocent Cardiac Murmurs
Definition also called functional murmers
1. Abnormal sounds caused by turbulence of blood at the origin of the great vessels
2. Murmurs not associated with structural or hemodynamic abnormalities
3. Accentuated in high cardiac output states, febrile illness and anemia

Incidence
30% of children below the age of 5 years

Examples
1. Classic vibratory murmur (Still's murmur), on lower left sternal border.
2. Physiological pulmonary flow murmur: on upper left sternal border.
3. Carotid Bruit, right supraclavicular and over the carotids, occasionally with a thrill
4. Jugular venous hum, right or left supra or infra-clavicular area, inaudible in the supine
position

71
 Pediatric Hypertension

Definition
■ Hypertension: Systolic and /or diastolic BP > 95th % for age and sex on at least 3 occasions
■ White-coat hypertension: Hypertension only in health care facilities

Stages of hypertension
■ Normal: < 90 th percentile
■ Pre-hypertension: Systolic and/or diastolic BP between 90 th percentile and 95th
percentile
■ Stage 1 hypertension: between 95th percentile and 99th percentile
■ Stage 2 hypertension: > 99 th % percentile plus 5 mmHg or more

Measurement of blood pressure

1. Bladder width: should cover about 70% of the upper arm length
2. Bladder length: should encircle the arm completely
3. Use the wrong cuff size can lead to wrong BP readings (small cuff overestimates BP)
4. BP should be measured in both arms and legs to rule out coarctation of the aorta
5. Blood pressure should be measured in at least 3 separate office visits with 1 week apart

72
Etiology
1. Renal HTN
a. Renal parenchymal disease: CKD, reflux nephropathy, renal scarring
b. Renovascular: Renal artery stenosis ,--------------------
1
Hypertension in
children J
i is usually secondary
renal !
2. Coarctation of the aorta > I
------------------------------------------------------------------------------------------------------------------------------ I_____________________

3. Endocrinal causes
a. Cushing syndrome
b. Congenital adrenal hyperplasia

4. Catecholamine excess
c. Pheochromocytoma: Paroxysmal hypertension is characteristic
d. Neuroblastoma

5. Iatrogenic : Corticosteroid therapy

6. Increased ICP
7. Essential hypertension
8. Pain

Clinical Picture
- Picture of the cause
- Headache, vomiting, difficulty initiating sleep, daytime tiredness,
- HTN retinopathy: coma, convulsions
- Failure to thrive and cardiac failure are the most common features in infants

Investigations
1. Kidney function tests (Creatinine, BUN)
2. Uric acid, urine analysis and culture
3. Electrolytes (Na, K),
4. Fasting glucose
5. Fasting lipids profile
6. Abdominal sonar, echo, renal Doppler

Treatment
- Treatment of the cause: coarctectomy...
- Life-style modification and Anti-hypertensive drugs:
■ Indications: Severe symptomatic HTN, secondary HTN, insufficient response to
life style modification.
■ Preferred medications: Diuretics, B blockers, ACE-I and calcium channel blockers

73
 Acute congestive heart failure

Definition
The heart fails to do its function as a pump:
■ Pumping blood into the circulation (■> low cardiac output)
■ Pumping blood from the systemic venous and pulmonary circulation (■ ♦ systemic and
pulmonary congestion
In acute congestive heart failure, the clinical manifestations are
■ Acute
■ Evident at rest
■ May rapidly progress to acute pulmonary edema or cardiogenic shock

Normal cardiac performance depends on

1. Preload : volume load on the right side of the heart
2. Contractility: myocardial contractility
3. Afterload: pressure load on the left side of the heart
4. Heart rate and rhythm: how fast and hoe regular the heart rate is

Hypertensive Coarctation
Contractility heart failure of the
aorta
Etiology
Preload failure (increased volume load on the right side of heart)
1. Hypervolemia: acute renal failure and over infusion
2. Big left to right shunts e.g. PDA, VSD

Contractility failure (poor myocardial contractility)

1. Myocarditis (infective-rheumatic).
2. Myocardial ischemia and myocardial infarction
3. Cardiomyopathy
4. Negative inotropic factors: hypoxia, hypoglycemia and acidosis.
After load failure (pressure load on the left side of the heart)
1. Systemic hypertension
2. Severe Aortic stenosis.

74
3. Severe coarctation of the aorta.

Arrhythmic failure:
1. Severe tachycardia e.g. Paroxysmal supraventricular tachycardia
2. Severe bradycardia

Clinical grading
1. Grade 1: (heart failure only): 3Ts
a. Tachycardia: compensatory mechanism
b. Tachypnea: pulmonary congestion.
c. Enlarged tender liver: systemic congestion.
d. Cardiomegaly

2. Grade II: heart failure and pulmonary edema (respiratory failure)

Heart failure with:
a. Severe respiratory distress, hypoxia ± central cyanosis
b. Chest crepitations (bilateral fine basal then course bubbling)
c. Chest X ray : Marked pulmonary congestion, pulmonary edema
d. ABG : hypoxia and + hypercarbia

3. Grade III: heart failure and circulatory failure (cardiogenic shock):

Heart failure, usually with severe respiratory distress ± central cyanosis, and:
a. Uncompensated low cardiac output peripheral hypoperfusion at rest (see shock)
b. Hypotension and vital organ hypoperfusion can lead to multi organs system failure (MOSF)
c. Severe distress (cyanosis)
d. Signs of shock including signs of poor peripheral perfusion and MOSF

Investigations
1. Chest x ray.
2. ECG: to diagnose arrhythmia.
3. Echocardiography: chamber size and cardiac anomalies.
4. Laboratory: arterial blood gas, CBC, ESR, CRP, ASOT and cardiac markers (Creatine kinase-
MB and troponin )

75
Management of acute congestive heart
failure
Treatment of heart failure: grade I
1. Supportive measures
■ Rest in semi sitting position
■ Fluid restriction to 60-70%
■ If distressed, IV fluids are used initially.
■ Then, nasogastric tube feeding, oral when tolerated
■ Salt restriction
■ Oxygen therapy: to reduce distress and correct hypoxia o Given warm and humidified
by mask or nasal prong
o Initial FiO2: 40% - 60%.

2. Digoxin therapy to improve myocardial contractility

Digoxin: (increase cardiac contractility)
■ Digitalizing dose: IM or IV 0.05mg/kg (given in 3 doses over the first 24 hours)
■ Maintenance dose: O.Olmg/kg/day in 2 divided doses; IM or IV, oral when tolerated
■ Neonates and small infants require lower doses
3. Diuretic therapy: Furosemide (Lasix) to reduce preload
■ IM or IV l-2mg/kg/dose/ 12 hours
■ Shift to oral if tolerated
■ Monitor K and avoid hypokalemia
4. After load reducing agents
■ ACE inhibitors as Captopril 0.5-2 mg/Kg/day in 2-3 divided doses

Treatment of pulmonary edema: grade II as grade I

but
1. Pre load reduction Diuretics: IV, higher doses and can use vasodilators as
nitroglycerin infusion
2. Inotropes: IV digoxin and can use others as dobutamine
3. Continuous positive airway pressure (CPAP) or mechanical ventilation according to
severity.

Treatment of cardiogenic shock: grade

III
1. Inotropic drugs (IV dopamine or dobutamine IV or both o rIV milrinone ) not digoxin as
it is slowly acting and high risk of toxicity
2. After load reducing agents(vasodilators):Captopril : 0.5 to 6 mg/kg/day in 2 to 4 doses

Specific treatment according to the causative disease e.g. rheumatic fever.

76
 The Respiratory Tract
The upper airways or upper respiratory tract
It includes the nose and nasal passages, paranasal sinuses, the pharynx, and the
portion of the larynx above the vocal folds (cords).

The lower airways or lower

respiratory tract
It Includes the portion of the larynx below the vocal folds, trachea, bronchi,
bronchioles and
alveoli.

Respiratory System
Capillary beds

Connective tissue-------

Frontal smus —

Sphenoid smus—
Nasal cavity---

Nasal vestibule Alveolar duct

Oral cavity
Mucous
Pharynx
Mucosal lining
Epiglottis

Vocal fold Pulmonary veto Alveol

Thyroid cartilage i
Pulmonary artery
Cncoid carriage Atrium

Trachea

Apex

Superior lobe Supenor lobe Lingular

Lobar bronchus division bronchus Carina of

Right superior trachea

Intermediate bronchus Mam

Right inferior
Horizontal fissure bronchi (right and left) Lobar
bronchus Left supenor Left

Oblique fissure inferior

Oblique fissure Cardiac notch
Middle lobe
Lingula of lung Inferior lobe

Inferior lobe

Diaphragm

77
 Upper Respiratory Tract Infections

1. Infections of the upper respiratory tract are a very common problem.

2. Children have a median of five upper respiratory tract infections (URTIs) per year in the
first few years of life, but some toddlers and primary school-aged children have as many
as 10-12 per year.
3. The term URTI embraces a number of different conditions:
■ Common cold (coryza)
■ Sore throat (pharyngitis, including tonsillitis)
■ Acute otitis media
■ Sinusitis (relatively uncommon)

4. The most common presentation is a child with a combination of these conditions. Acute
nasopharyngitis (common cold) is the most common. Otitis media and tonsillitis come
next. Nasal discharge, earache and sore throat are the main presentations.

1. Nasopharyngitis
- Acute nasopharyngitis (common cold or coryza) is the commonest infection in children.
- Unlike adults, the infection in infants and children usually involves the sinuses,
nasopharynx (nasopharyngitis) and middle ear.

Causative organisms:
■ The illness is mostly viral (rhinoviruses, coronaviruses and several other viruses).
■ But bacterial infections also occur (pneumococcal, staphylococcal, hemophilus influenza,
pertussis and several other bacteria).

Clinical picture:
1. Fever. The onset is usually sudden with low-grade fever, irritability and sneezing. Fever
may be absent. High fever should suggest complications as otitis media or sinusitis.
2. Nasal discharge. It begins within a few hours of onset. It is usually watery during the first
few days, and then it turns to mucoid for another few days. Nasal obstruction may be
severe especially in infants and it may interfere with feeding.

78
3. The course is benign in the majority of cases. Fever subsides within 2 days and nasal
discharge over a week. However, nasal discharge may remain as long as 2 weeks.

Complications:
Complications should be considered in the presence of high fever, significant cough or
persistent nasal discharge (more than 10 days).
1. Spread of infection to ears and sinuses (otitis media, sinusitis).
2. Acute bronchitis.
3. Serious lower respiratory infections (acute bronchiolitis, bacterial pneumonia).
4. It may be the prodromal stage of measles or whooping cough.
5. Precipitation of an asthmatic attack in asthmatic patient.

Treatment:
1. Infants with significant nasal obstruction interfering with feeding can use nasal
decongestants.
2. Antipyretics for associated fever may be used, (Antibiotics are of no benefit except if
bacterial infection suspected).

79
 2. Acute tonsillitis
- Tonsillitis is a common infection in children above the age of 2 years.
- Streptococcal pharyngitis and viral pharyngitis are the 2 main causes.
- Other uncommon causes are diphtheria and infectious mononucleosis (see specific
infections).

A. Streptococcal pharyngitis:

It is a common infection in children above the age of 2 years with peak incidence between
4-7 years.

Clinical picture:
The onset is abrupt with high fever, severe sore throat, vomiting and abdominal pain.

Throat examination reveals:

1. Diffuse redness of the tonsils and anterior pillars.
2. Follicular exudation (follicular tonsillitis) or membranous exudation
(membranous tonsillitis) are common and usually involving both tonsils.
3. Tender anterior cervical lymphadenitis is an early common finding.

1. Early complications as peritonsillar abscess.

2. Late autoimmune complications as rheumatic fever or poststreptococcal
glomerulonephritis may
occur.

Treatment:
1. Oral penicillin (50.000 unit/kg/day) or oral erythromycin (50 mg/kg/day) for 7-10 days.
2. Antibiotics are often prescribed for severe pharyngitis and tonsillitis.
3. In order to eradicate the organism completely (and prevent rheumatic fever) 10 days of
antibiotic treatment is required for pharyngitis or tonsillitis.

80
B. Viral pharyngitis:
The onset is usually acute with mild to moderate fever.

Clinical picture:
1. Sore throat is moderate and usually occurs 1-2 days after onset.
2. Throat examination reveals mild erythema of tonsils and pillars.
3. Small ulcers on the soft palate or posterior pharyngeal wall may occur.
4. Follicular tonsillitis is rare.
5. Rhinitis, cough, conjunctivitis and hoarseness are common associated findings.

- Pain is best treated with paracetamol or ibuprofen.

3. Otitis media
- Acute inflammation of the middle ear is a common complication of acute nasopharyngitis
especially in late infancy and early childhood (6 months to 6 years).

Causative organisms:
1. The illness is mostly bacterial and can be caused by gram-positive or gramnegative
bacteria.
2. Two organisms (streptococcus pneumonia and hemophilus influenza) account for 50%
of cases.
3. Other common organisms are Moraxella catarrhalis, streptococcus pyogens,
staphylococcus aureus and pseudomonas aeruginosa.

Clinical picture:
1. The illness starts acutely, few days after the onset of nasopharyngitis:
2. Fever and earache: Any febrile patient with unexplained irritability or excessive
crying should be examined for otitis media.
3. Ear discharge (otorrhea): May occur with drum perforation.
4. Ear examination with otoscope reveals a congested bulging eardrum.

AOM

81
Complications of otitis media

Ear Skeletal Neurological

■ Drum perforation (acute ■ Acute or chronic mastoiditis* Meningitis or focal otit
or chronic) swollen, painful & encephalitis
■ Chronic suppurative erythematous mastoid area ■ Acute cerebral
otitis media (hearing ■ Petrositis: infection of thrombophlebitis (acut
loss) the pneumatized cells hemiplegia)
■ Chronic secretory of temporal bone ■ Acute labyrnthitis (acui

otitis media (hearing ataxia)

loss) ■Acute facial palsy

Otitis media with Otitis media with effusion and

effusion grommet

Treatment:
- An oral broad-spectrum antibiotic (as ampicillin,50 mg/kg/day) to cover both gram-
positive and gram-negative organisms is prescribed for 7-10 days.

82
 Lower Respiratory Tract Infections

Infections of the lower respiratory tract are a common potentially serious problem.
- Acute bronchitis, acute bronchiolitis and pneumonia are the three most common problems.
- Other infections as lung suppuration and pulmonary tuberculosis are less common.
- Cough and/or respiratory distress are the two main clinical presentations.

Lower respiratory tract

Acute bronchitis is by far the most common cause of acute cough in children.

Causative organisms:
■ Nonspecific bronchitis is mostly viral following nasopharyngitis.
■ Bacterial infections (pneumococci, streptococci, staphylococci, hemophilus influenza) also
occur especially in early infancy, with malnutrition and with immunodeficiency.
■ Specific bronchitis: with measles, pertussis, diphtheria and scarlet fever.

Clinical picture:
1. It is mostly preceded by nasopharyngitis, few days before the onset.
2. The onset is gradual with dry cough and chest discomfort. Fever is common in young
children but it may be absent.
3. Bacterial infection is considered if:
. High or persistent fever

83
 . Patient looks sick/toxic
. Prolonged cough

4. The course of illness can be divided into 3 stages, each for few days:
a) Early stage During the first few days
■ The cough is dry, severe, metallic (brassy) and may be spasmodic (tracheitis).
■ During this stage, chest examination is unrevealing and diagnosis depends entirely on
the characters of cough.
b) Productive stage During the next few days
■ Cough becomes productive and less severe and the chest becomes rattling.
■ Chest examination reveals palpable rhonchi, expiratory rhonchi, and moist crepitations.
c) Convalescent stage.
■ During the last few days, cough decreases in frequency and severity and
■ Chest signs disappear gradually.
■ It is not unusual for simple bronchitis to remain as long as two weeks.

Treatment:
1. Most cases of acute bronchitis are viral in origin and recover spontaneously without any
therapy.
2. However, drugs may be used in certain situations.
■ Cough medicines: Cough suppressants should be generally avoided but they may
be used then the cough is severe and too frequent.
■ Antibiotics: (in bacterial infections only). An oral broad-spectrum antibiotic as
ampicillin or amoxicillin (50 mg/kg/day) for 7-10 days is sufficient.

Common causes of cough in infancy and childhood

Acute cough (duration less than 2 weeks)

■ Without respiratory distress: Acute bronchitis, laryngitis, and sinusitis.
■ With respiratory distress: Acute bronchiolitis, pneumonia, and acute asthmatic attack.
Prolonged cough (duration is 2 weeks to 2 months)
■ Complicated bronchitis (bacterial bronchitis, segmental collapse, pneumonia).
■ Sinusitis (due to postnasal discharge).
■ Pertussis (whooping cough) and pertussis-like illness.

Chronic cough (duration more than 2 months)

■ Chronic infections (pulmonary tuberculosis, bronchiectasis). Chronic or persistent asthma.
Recurrent aspiration.

84
 Pertussis (whooping cough)
Causative organism:
Bordetella pertussis (coccobacilli). With compulsory vaccination in infancy, the disease has
become relatively uncommon.

Clinical picture:
The possibility of pertussis should be considered in cases of prolonged cough.
1. Catarrhal stage (1-2 weeks):
It starts with nasopharyngitis, fever and cough, which increases gradually increases
in frequency and severity and becomes more at night.

2. Paroxysmal stage (2 -4 weeks)

■ This stage is characterized by paroxysmal attacks of severe spasmodic cough
characteristically more at night.
■ During an attack, a series of forceful cough (5 -10) during one expiration occurs.
■ The attack ends with sudden forceful inspiratory crow (whoop) and followed by
vomiting or coughs of large amount of thick mucoid sputum.

3. Convalescent stage (1 -2 weeks)

The number and severity of paroxysms decrease and vomiting becomes less
frequent

2. Pneumothorax
3. Activation of latent tuberculosis may occur.

Laboratory confirmation:
■ Leukocytosis (above 20.000) with absolute lymphocytosis.
■ Rapid antigen detection or culture from nasal swab

Treatment:
1. Erythromycin (50 mg/kg/day, oral) is the drug of choice.

Pertussis-like illness in properly vaccinated infants or children should suggest other

causative agents especially adenovirus infection. In this situation, lymphocytosis is also present
but usually not marked as in pertussis.

85
 2. Acute bronchiolitis

Incidence
■ Acute bronchiolitis is a common lower respiratory tract infection that occurs during the
first 2 years of life, with peak incidence at 6 months of age.
■ It is the most common cause of respiratory distress and wheezing in infants.
■ It causes inflammatory obstruction of the small airways, leading to bronchiolar
obstruction, air trapping and hyperinflation.

Causative organisms:
1. It is a viral illness, mostly caused by respiratory syncytial virus (RSV).
2. Parainfleunza virus and adenoviruses may be responsible in some cases.
3. The source of infection is usually a family member with minor respiratory illness.

Clinical picture: (3 stages)

1. Prodromal stage: Mild URI with nasal discharge and sneezing for few days.
2. Respiratory distress and expiratory wheezing: Manifestations of respiratory
distress (rapid respiration and retractions) with paroxysmal wheezy cough become
evident. Chest auscultation reveals expiratory wheezing. This stage usually lasts for few
days.
3. Rapid recovery usually occurs within few days. The case fatality rate is less than 1%.

Investigations:
1. Chest X-ray: hyperinflation of the lungs with focal atelectasis.
2. Blood gas analysis; hypoxia- CO2 retention.
3. RSV antigen detection from nasopharyngeal secretions.

Treatment:
1. Infants with minimal or mild respiratory distress (at home)
a) Close observation: Increasing distress is an indication for hospitalization.
b) Drugs as cough medicines and bronchodilators are generally not helpful.
c) Careful feeding to avoid aspiration.

86
 2. Infants with moderate to severe respiratory distress (at hospital)
a. Oxygen therapy to correct hypoxemia.
b. I.V maintenance fluid therapy to prevent dehydration.
c. Nebulized salbutamol may be used and some infants may benefit.
d. Corticosteroids are not beneficial and antiviral agents (as ribavirin) are not necessary.
e. Mechanical ventilation may be rarely used in those with severe respiratory failure not
responding to the above measures (see Pediatric emergencies).

3. Pneumonia
Definition
- It is a common, serious lower respiratory tract infection characterized by an acute
inflammatory consolidation of alveoli, infiltration of interstitial tissue with inflammatory cells or
a combination of both.
- Most cases are caused by bacterial or viral infections.

Etiology
Infectious pneumonia

■ Bacterial:
- Gram +ve: pneumococci, streptococci, staphylococci.
- Gram -ve: H. influenza, klebsiella, pseudomonas
- TB
■ Parasitic: Loffler's pneumonia
■ Viral:
- RSV (most common)
Adenovirus
■ Mycotic:
- Aspergillosis
- Candidiasis

■ Other microorganisms:
- Actinomyces - Pneumocystis carnii-
- Chlamydia and Mycoplasma

Non infectious pneumonia

1. Aspiration and chemical (amniotic contents, vomitus, or kerosine or foreign body).

2. Hypostatic pneumonia

Pathological types
1. Lobar

87
 ■ Unilateral affection of one or more lobes.
• Etiology: It is mostly bacterial
■ X ray : Chest x-ray shows lobar consolidation
Bronchopneumonia
2.
■ Bilateral affection of both lungs with small foci.
■ Etiology: bacterial or viral.
* Chest x-ray shows fine nodular or patchy infiltration.
Interstitial
3. ■ Bilateral affection of interstitial lung tissues.
• Etiology: mostly viral.
* Chest x-ray: parahilar shadow with radiating streaks

Rt upper lobar pneumonia Rt middle lobar pneumonia Bilateral bronchopneumonia

Recent classification of pneumonia:

1. Pneumonias occurring in usually healthy individuals are community-acquired pneumonias.
2. Pneumonias occurring in patients who are hospitalized or living in an institution such as a
nursing home are called hospital acquired or nosocomial pneumonias

Clinical picture:
n
Symptoms
■ Pneumonia should be suspected in every case of respiratory distress, fever and
cough
■ Difficult feeding and referred pain (neck or abdomen)
n
Signs

1. Manifestations of respiratory distress include:

Grade I: Tachypnea (rapid respiration).
Grade II: Intercostal and subcostal retractions
Grade III: Expiratory grunting.
Grade IV: Cyanosis appears.

2. According to pathological types

a. Lobar pneumonia

88
 ■ Bronchial breathing over the involved lobe is the main finding.
■ Some dullness to percussion over the involved lobe may be present.
b. Bronchopneumonia
■ Fine bilateral consonating crepitations are the main finding.
c. Interstitial pneumonia
■Severe spasmodic cough and tendency to expiratory wheezing are the main
findings.

3. Diagnosis of the causative

organism

Bacterial pneumonia Viral pneumonia

igh grade fever and severe course Low grade fever
levated ESR, CRP, leukocytosis Mild or no elevation of
laboratory tests
ray: lobar pneumonia X ray Interstitial pneumonia
Common complications Less common complications

Complications
1. Respiratoryfailure
The most serious complication and the main cause of death.
2. Pleural effusion
With bacterial pneumonias especially pneumococcal, staphylococcal pneumonia.
3. Lung abscess and peumatoceles
With bacterial pneumonia especially staphylococcal pneumonia.
4. Myocarditis and acute heart failure
Especially in infants with severe bacterial pneumonia.

Investigations:
1. Chest x ray:
a. Confirm the diagnosis
b. Complications: effusion - empyema - pneumatocele - lung abscess.
2. Blood gas: in severe cases lowered 02 tension and raised C02
3. Complete blood count, ESR, CRP: DD/ bacterial and viral causes
4. Culture and sensitivity test: morning nasopharyngeal aspirate or sputum culture.

Treatment:
A. Hospital management (7-10 days):
1. Indications
■ Severe pneumonia (severe RD) or complicated pneumonia
■ Small infants (Less than 6 months)
2. Supportive measures:
- Humidified oxygen - IV fluid (NPO) - suction - mechanical ventilation
3. Specific treatment:

89
 Broad spectrum combined parenteral antibiotics to cover G+/-
(Ampicillin 50- 100 mg/kg/day + gentamycin 4-6 mg/kg/day).
Antibiotics may be changed according to results of culture and sensitivity and clinical
response.
4. Treatment of complication:
Drainage of empyema.
Mechanical ventilation (in respiratory failure)

B. Home management for most cases:

1. In Older children with mild pneumonia without distress.
2. Oral or better intramuscular antibiotics.
3. Amoxicillin 50 mg/kg/day or better broader-spectrum antibiotics such as amoxicillin-
clavulanic acid for 7-10 days.

What is atypical pneumonia?

■ Atypical pneumonia is an infection affecting the lower respiratory tract.
■ People with atypical pneumonia have different symptoms than those with typical
pneumonia. These might include a prominent headache, a low-grade fever, an earache,
and a sore throat.
■ Symptoms of atypical pneumonia tend to be milder and more persistent than those of
typical pneumonia.
■ Atypical pneumonia requires different antibiotics than typical pneumonia, Mycoplasma
usually respond to macrolide for 7-10 days

Causes
1. Mycoplasma pneumoniae usually infects people under 40 (common in school-aged
children) with mild pneumonia symptoms. It commonly causes earaches, headaches,
and a sore throat, as well.
2. Chlamydophila pneumoniae is common in school-aged children and young adults.
3. Legionella pneumophila is more severe, and seen most often in older adults, people who
smoke, and those with weakened immune systems.

Legionella pneumonia

with mycoplasma pneumoniae

90
 Suppurative Lung Diseases

1-Purulent pleurisy (Empyema)

Definition
Empyema means accumulation of pus in the pleural spaces.

Causes
■ Complication of bacterial pneumonias: Common organisms include Pneumococci,
Staphylococci & Hemophilus Influenza
■ Contamination introduced from chest trauma or surgery
■ Mediastinitis
■ Rupture of lung abscess or sub diaphragmatic abscess

Clinical picture
■ Symptoms
Symptoms consist mainly of dyspnea, fever, and chest pain exaggerated by deep
breathing, cough or straining. The child often lies on the affected side
■ Signs
- Chest signs include diminished movement of the affected side and shift of the
trachea and mediastinum to the opposite side.
- Dullness on percussion
- Diminished breath sounds

Complications
- Bronchopleural fistula.
- Chronicity: pleural fibrosis resulting in limited chest expansion.

Investigations
- Chest X-ray: unilateral (or bilateral) massive homogenous opacity with
obliterated costophrenic angle and mediastinal shift to the opposite side.
- Thoracocentesis and culture of pus may reveal the causative organism.

Treatment
1. Immediate closed drainage of pus by an underwater seal or by continuous suction.
2. Systemic antibiotic therapy: For 3-4 weeks according to culture- sensitivity studies.

91
 2- Lung abscess
Definition
It is a suppurative process resulting in destruction of the pulmonary parenchyma with formation
of a cavity containing purulent material.
It may be acute (less than 6 weeks duration) or chronic (more than 6 weeks duration).

Etiology:
A. Aspiration of infected material or foreign body.
B. Secondary to:
■ Pneumonia: It may complicate pneumonia caused by aerobic pyogenic bacteria (Staph.
Aureus, Klebsiela, and Pseudomonus)
■ Bronchiectasis
- T.B.
■ Amoebic lung abscess: Rare cause in children.
■ Metastatic lung abscess: Uncommon in children and may occur secondary to septic emboli
from right-sided bacterial endocarditis or septic thrombophlebitis
Clinical picture:
Symptoms
It is characterized by an insidious onset with fever, anorexia, weight loss and cough often
associated with hemoptysis and copious amounts of foul smelling or purulent sputum followed by
marked relief of symptoms, dyspnea and chest pain.
Signs
- Respiratory distress, diminished air entry, localized bronchial breathing.

Complications:
■ Empyema or pneumothorax.
■ Bronchiectasis.
■ Spread of infection (local or systemic).

Investigations:
1. Chest X ray or better CT: Reveals a cavity with or without air fluid level inside
surrounded by consolidation.
2. Sputum culture and sensitivity studies.
3. Bronchoscopy and BAL culture.

92
Treatment:
1. Prolonged antibiotic therapy for 6 weeks according to culture - sensitivity.
2. Bronchoscopy: It is indicated only to identify and remove a foreign body.
3. Resection of the affected lobe: It is indicated in children with recurrent severe hemoptysis
or for chronic cases.

3- Bronchiectasis
Definition
Bronchiectasis is a condition characterized by dilatation of the bronchi with inflammatory
destruction of the bronchial and peribronchial tissues and accumulation of exudative material
in the dependent bronchi and sometimes their distension.

Etiology
A. Congenital bronchiectasis:
It is due to maldevelopment of bronchi (rare).

B. Acquired bronchiectasis:
Usually occurs due to chronic pulmonary infection. Predisposing factors include:
1. Foreign body
aspiration.
2. Enlarged broncho-pulmonary nodes due to TB.
3. Lung abscess or localized cysts.
4. Immotile cilia syndrome
5. Cystic fibrosis
6. Asthma.
7. Immune deficiency
8. Gastroesophageal reflux
disease

Pathological changes
They include the following:
1. Destruction of the ciliated epithelium with loss of elastic tissue.
2. Thickening of the bronchial walls due to interstitial edema and fibrosis.
3. Distortion of the bronchial walls with formation of spherical, cylindrical or fusiform
cavitary spaces, which become full of stagnant pus resulting from infection. With a
vicious cycle of infection, inflammation and destruction.
4. The mainly affected areas are the basal segments of the lower lobes, the right middle
lobe and the lingular segment of the left upper lobe.

Classification of Bronchiectasis
Anatomic classification Etiological classification
a) Localized (one lobe) a) Cystic fibrosis bronchiectasis
b) Generalized disease (diffuse). b) Non-cystic fibrosis bronchiectasis

93
Clinical picture
Symptoms
1. -Fever, anorexia, and poor weight gain are common.
2. Chronic cough with expectoration of copious fetid mucopurulent sputum, usually changing
with posture.
3. Hemoptysis may occur.
Sl&ns
1. Chest signs: Moist or musical rales may be heard over the affected area as well as signs of
consolidation or fibrosis.
2. Clubbing of fingers is usually seen.
3. With extensive bronchiectasis, there is persistent dyspnea and delayed physical growth.

Complications:
1. Pulmonary hypertension that may be complicated by cor-pulmonale.
2. Respiratoryfailure.

Investigations:
1. Chest X-ray: may show honeycomb or soap bubble appearance.
2. CT scan of the chest confirms the diagnosis.

Treatment:
1. Effective Postural drainage and chest physiotherapy.
2. Antibiotic therapy (oral, parenteral or aerosol) according to culturesensitivity studies.
3. Bronchodilators and symptomatic management.

4. In cases of localized bronchiectasis, lobar resection should be considered.

94
- Tuberculosis is one of the most serious diseases in childhood.
- Mycobacterium tuberculosis is the main causative organism.
- Other organisms as Mycobacterium bovis and mycobacterium Africanum are of major
pathogenic importance.

1. Primary infection:
a. The lung is the portal of entry in over 98% of cases. Other areas of primary infection
are the skin, tonsils and gut.
b. The local infection "Gohn's focus" spreads locally and to the lymph nodes, together

these constitute the primary complex.

c. Most such lesions heal slowly by fibrosis and may calcify. Complications may arise from
local progression of the primary complex especially in the lungs.
Complications:
1. Local spread.
2. Bronchogenic spread.
3. Hematogenous spread causing miliary tuberculosis.
4. Pleural effusion: In older children as a hypersensitivity reaction.
5. Empyema, caseation and cavitation: More often in malnourished children.

F
Clinical manifestations of Pulmonary TB
■ General symptoms: Loss of appetite, loss of weight, night sweat and night fever.
■ Chronic cough: It is the main symptom. Sputum may be mucoid, purulent or blood
stained. The patient may complain of localized wheezing, recurrent colds or
pneumonia for a number of months before diagnosis, with no response to routine
treatment.
■ Chest signs: They vary according to the pathological lesion:

95
 a. In pneumonic lesions, there may be signs of consolidation.
b. In pleural effusion, physical signs of effusion may be detected.
c. In fibrosis, deviation of the trachea and mediastinum to the same side occurs.
d. In compression of the trachea and bronchi by tuberculous lymph nodes, wheezes
may be noticed and the condition should be differentiated from bronchial asthma.

Diagnostic investigations
■ CBC: Lymphocytosis
■ ESR: Very high ESR usually abovelOO.
■ Tuberculin test: Mantoux test is the most important immunological diagnostic tool.
■ Isolation and culture of organism;
D
Get sputum or morning gastric aspirate
a
Direct smear with ZN stain
D
Culture on a Lowenstein Jensen medium (4 weeks)
D
BACTEC culture (10 days only)
■ Quantiferon TB test; (good negative test)
■ Biopsy of lymph nodes or pleura: For pathological study
■ .Radiological studies: Chest x-ray and chest computed tomography (CT scan).
■ Recent methods for diagnosis: Usage of ELISA and PCR (polymerase chain reaction).

Tuberculin test
0.1 ml purified protein derivative is injected intradermally in the skin of the flexor surface of
the forearm. The reaction should be read at 48-72 hours.
Induration (and not erythema) is measured in mms in the longitudinal as well as the
transverse diameters and the mean reading is recorded.
An induration less than 5 mms is considered negative.
An induration measuring 5-9 mms is considered doubtful and should be repeated.
An induration of 10 mms or more is considered positive.

1. BCG vaccination: The reaction never exceeds 15 mm induration. Positiv

e
2. TB infection: It is considered in 2 situations:

96
 o Positive reaction in a child less than 5 years who is not BCG vaccinated, o
Strongly positive reaction (over 15mms) in previously vaccinated child.

False positive test False negative test

■ BCG vaccine 1. Subcutaneous injection or use of
■ Infection with atypical outdated tuberculin.
mycobacteria (leprosy) 2. Recent use of corticosteroids or
immunosuppressives.
3. Intercurrent infections especially viral
ones.
4. Recent antiviral vaccines (especially
measles and mumps).
5. Advanced disseminated TB, chronic
debilitating disease with cachexia and
cell mediated immune deficiency.

Prevention of Tuberculosis

1. General methods: They include the following:

1. Good nutrition, good housing and better aeration.
2. Elimination of TB in cattle and pasteurization of milk.
3. Mass radiography centers for early diagnosis and treatment
4. Repeated examination and radiography of employees who deal with children in
hospitals, schools and nurseries to detect diseased persons.

2. BCG Vaccination:
- This is the cheapest and most effective way for prevention of TB.
- It should be administered as early as possible to infants (in the first month of life).
- It is a live attenuated vaccine given intradermally in a dose of 0.1 ml usually opposite
the insertion of the left deltoid muscle.
- The reaction from the vaccine normally develops after 3-6 weeks with erythema, papule
formation and occasional superficial ulceration. It subsides within the following 2-6
months leaving a small scar.
- A booster dose is administered at 6 years.

97
■ Chemoprophylaxis:
When an individual has to live near a tuberculous contact for variable periods, isoniazid is used
in a dose of 15 mg/kg/day for 6 months to one year.

Treatment
Chemotherapy of tuberculosis
- It usually consists of combined drug therapy to delay the emergence of drug resistant
strains.
- Drugs are classified into first and second lines or alternative drugs.
- Treatment starts with 2 or 3 first line drugs and for at least 6-9 months.

Antituberculous drugs

First line drugs

Isoniazid (INH):
Rifampicin or Rifampin (RIF):
Pyrazinamide (PZA): 10 -15 mg/kg/day ... oral.
10 - 20 mg/kg/day ... oral.
Alternative drugs 20 - 40 mg/kg/day ... oral.
Streptomycin (STM):
Ethambutol (ETB):
Ethionamide (ETH):
20-40 mg/kg/day... I.M.
Other drugs (Kanamycin, amikacin, para-aminosalicylic acid).
15-20 mg/kg/day... oral.
15-20 mg/kg/day... oral.
Antituberculous regimen

■ In the first 2 months: isoniazid + rifampicin + pyrazinamide.

■ In the following 4 months: isoniazid + rifampicin only.

Indications of corticosteroids In TB
Steroids may be used with anti-TB drugs in the following situations:
■ Allergy to antituberculous drugs.
■ TB serositis: Pleurisy, serous pericarditis, ascitic type of TB peritonitis.
■ In miliary TB affecting the suprarenal glands.
■ In endobronchial TB after removal of the glands to avoid postoperative stricture.
■ After surgical removal of cervical TB lymph nodes to avoid fibrous tissue
formation.

98
Extra-pulmonary Tuberculosis
1. TB lymphadenitis
Mi;
Cervical lymph nodes are most commonly affected.
Initially lymph nodes are discrete, mobile and not tender
Then, nodes are matted and adherent to the deep
structures with cold abscess formation

2. Skeletal TB
• TB of the spine (Pott's
disease)
Lower thoracic vertebra followed by lumbar, then cervical regions is affected.
It affects the body of one or more vertebrae resulting in bone destruction
Pain, kyphosis and compression paraplegia
• X ray: rarefaction and destruction of the vertebrae.

* TB arthritis
Large joints (hip, ankle, knee and elbow).
Pain with limitation of movement
■ X ray: rarefaction and destruction of the bone near the
the affected joint.
3. Abdominal TB
■ TB enteritis (primary or secondary)
• Chronic diarrhea with tenesmus and bleeding.
• Stools are white and greasy (malabsorption).

• TB peritonitis : caused by direct extension from mesenteric lymph nodes

• Ascitic :- fluid with high protein content and lymphocytes
• Caseous:- doughy sensation of the abdomen.
• Adhesive:-Loops of intestine are glued together by fibrinous adhesions.
• Encysted :-small effusion and caseous masses are encysted between adherent loops

■ Tuberculous mesenteric lymphadenitis (Tabes mesentrica)

• Enlarged matted glands palpable in the right iliac fossa

• Urogenital TB
Renal tuberculosis: results from hematogenous spread of TB bacilli.
Bacilli are released in urine and may spread to the renal pelvis, ureters, bladder, Urine
examination reveals sterile pyuria but culture may be positive
4. TB oftheCNS
»TB meningitis
Hematogenous in origin or with miliary TB.
• Headache, irritability, disorientation (due to increased intracranial tension). Convulsions
and focal neurological deficits.
CSF: increased protein and lymphocytes, decreased glucose and chloride
* Tubeculoma
Caseous lesion large enough to act as space occupying lesion
5. Other types
■ TB pericarditis: through lymphatic spread- diagnosed by echocardiography.
■ TB of the skin (lupus vulgaris) - TB of the eye and ear (chronic otitis media and mastoiditis

99
 Cystic Fibrosis

Definition:
Autosomal recessive mutation of cystic fibrosis transmembrane regulator (CFTR) gene
leading to abnormal ion transport across the epithelial cells of the exocrine glands of the
respiratory tract and pancreas results in increased viscosity of secretions.

Pathogenesis
■ In the lungs, viscid mucus in the smaller airways predisposes to chronic infection,
initially with Staph, aureus and H. influenza and subsequently with Pseudomonas
aeruginosa. This leads to damage of the bronchial wall, bronchiectasis and abscess
formation.

■ Over 90% of children with CF have malabsorption and failure to thrive from birth,
because of pancreatic exocrine insufficiency (lipase, amylase and proteases)

■ Abnormal function of the sweat glands results in excessive concentrations of sodium

and chloride in the sweat (60-125mmol/L in cystic fibrosis, 10-30 mmol/L in normal
children, equivocal in between).

Mutant CFTR Channel

Normal CFTR Channel

moves chloride ions to the
outside of the cell \__-

Clinical presentations of cystic fibrosis

Newborn
Diagnosed through newborn screening.

Infancy
■ Meconium ileus in newborns.
■ Prolonged neonatal jaundice.
■ Failure to thrive.

100
 ■ Recurrent chest
infections.
■ Malabsorption, steatorrhea

Young child
■ Bronchiectasis
■ Rectal prolapse
■ Nasal polyp
■ Sinusitis

Older child and adolescent

■ Allergic bronchopulmonary aspergillosis (ABPA)
■ Diabetes mellitus (often not insulin-dependent)
■ Biliary cirrhosis and portal hypertension
■ Distal intestinal obstruction (DIOS, meconium ileus equivalent)
■ Pneumothorax or recurrent hemoptysis
■ Sterility in males
■ Increasing psychological problems

o Symptoms:
■ Recurrent or persistent chest infections, the child has a
persistent loose cough with excessive purulent sputum.
■ Frequent large pale very offensive and greasy stools
(steatorrhea).
o Signs
■ Hyperinflation of the chest due to air trapping.
■ Coarse inspiratory crepitations and/or expiratory wheeze.
■ Finger clubbing.
■ Ultimately 95% of patients with CF will die of respiratory failure.
■ Failure to thrive

Diagnosis
■ The essential diagnostic procedure is the sweat test, to confirm that
the concentration of chloride in sweat is elevated.

Sweat chloride test

■ Sweating is stimulated by applying a low-voltage current to
pilocarpine applied to the skin.
■ The sweat is collected into a special capillary tube or absorbed onto
a weighed piece of filter paper.
■ Diagnostic errors are common if there is an inadequate volume of
sweat collected.
< 30 mmol/L = negative result

101
 30-59 mmol/L = borderline result if < 6 months old
40-59 mmol/L = borderline result if > 6 months old
> 60 mmol/L = consistent with CF.
Confirmation of diagnosis can be made by testing for gene abnormalities in the
CFTR protein

Management
- The effective management of CF requires a multidisciplinary team approacf
- All patients with CF should be reviewed at least annually in a specialist ceni
- The aim of therapy is to prevent progression of the lung disease and to
maintain adequate nutrition and growth.

A. Respiratory management
- Recurrent and persistent bacterial chest infection is the major problem.
In younger children, respiratory monitoring is based on symptoms; older
children should have their lung function measured regularly by spirometry.

■ Treatment of airway inflammation:

- Inflammation is a major component of the vicious cycle characterizing CF
pulmonary disease.
- Anti-inflammatory drugs for CF lung disease appear to have beneficial effects
on disease progression (corticosteroids, macrolide antibiotics, non-steroidal
anti-inflammatory drugs)

■ Antibiotics.
- Many CF specialists recommend continuous prophylactic oral antibiotics
(usually flucioxacillin), with additional oral antibiotics for any increase in
respiratory symptoms or decline in lung function.
- Persisting symptoms or signs require prompt and vigorous intravenous therapy
to limit lung damage, usually administered for 14 days.
- Chronic Pseudomonas infection is associated with a more rapid

102
 decline in lung function, which is slowed by the use of daily nebulized
antipseudomonal antibiotics.
■ Mucolytics.
- Nebulized DNase, hypertonic saline, or N-acetylcysteine may be helpful to
decrease the viscosity of sputum and to increase its clearance.
■ Physiotherapy.
- Children should have physiotherapy at least twice a day, aiming to clear the
airways of secretions.
■ Bronchodilators;
As reversible airway obstruction occurs in many children with CF.
■ Lung transplant:
- Bilateral sequential lung transplantation is the only therapeutic option for end-
stage CF lung disease.
- Outcomes following lung transplantation continue to improve, with over 50%
survival at 10 years.
- Meticulous assessment, for example, with regard to comorbidities and
microbiology, psychological preparation, optimal timing of transplantation,
and expert post-transplant care, are all essential parts of the multidisciplinary
transplant process.

B. Nutritional, GIT and hepatic management

■ Nutritional status should be assessed regularly.
■ A high-calorie diet is essential, and dietary intake is recommended at 150% of
normal.
■ To achieve this, dietary supplements oral, NG, or G-tube may be required.
Overnight feeding via a gastrostomy tube is increasingly used.
■ Most patients require fat-soluble vitamin supplements.
■ Pancreatic insufficiency is treated with oral enteric-coated pancreatic enzymes
replacement therapy taken with all meals and snacks. Dosage is adjusted
according to clinical response.
■ Oral bile acid therapy aimed at improving biliary secretion in terms of bile
viscosity and bile acid composition, is currently the only available therapeutic
approach for cystic fibrosis associated liver disease.
• Supplement with salt starting at diagnosis (oral rehydration fluid) is essential
particularly in hot environments.

C. Psychological support:
- The CF team should provide psychological and emotional support for CF patients
and their families.

D. Gene therapy:
- Despite early hopes, gene therapy has not yet proven to be a useful treatment
in CF.

103
 Pediatric Allergy
Definition
- This comprises asthma, allergic rhinitis, conjunctivitis, eczema, urticaria and
hypersensitivity to food, drugs and insect bites or stings
- These diseases are common as they are:
• Common, up to 40% of children develop allergic rhinitis, eczema and asthma and up
to 8% develop food allergy
• Are increasing in prevalence throughout the developed world
• Are a major cause of primary care and emergency hospital attendance
• Cause significant morbidity and can be fatal (asthma and anaphylaxis)

Age of presentation
- Allergic children develop individual allergic disorders at different ages:
o Eczema and food allergy in infancy
oAsthma and allergic rhinitis as toddlers and in childhood
- The presence of eczema or food allergy in infancy is predictive of asthma and allergic
rhinitis in later childhood
- This progression is referred to as the 'allergic march'
- Family history of allergy is usually positive

Mechanisms of allergic disease

- Many genes have been linked to the development of allergic disease
- Mutations in these genes lead to a susceptibility to allergy
- Allergic diseases occur when individuals make an abnormal immune response to
harmless environmental stimuli, usually proteins.
- The developing immune system must be ‘sensitized’ to an allergen
- However, sensitization can be ‘occult’, e.g. sensitization to peanut from exposure to trace
quantities of peanut
- Only a few stimuli account for most allergic disease:
> Inhalant allergens, e.g. house-dust mite, pollens, pet dander and molds
> Ingestant allergens, e.g. cow’s milk, nuts, soya, egg, wheat, seeds, legumes, seafood
and fruits
> Insect stings/bites
> Drugs and natural rubber latex

Prevention of allergic diseases (under trial)

• Environmental manipulation (avoidance of allergens in pregnancy or in infancy)
- Probiotics (orally administered microorganisms which alter intestinal microbiota)
- Prebiotics (immunologically active oligosaccharides)
- Nutritional supplements (e.g. antioxidants, fish oils, trace elements)

104
 Childhood Asthma
Introduction:
• Asthma is the most common chronic respiratory disorder in childhood
• There is a significant increase in the incidence of asthma over the last 40 years
• In some parts of the world asthma affects up to 18% of the population especially in children
and adolescents
• Asthma is an important cause of absence from school, restricted activity, and anxiety for the
child and family

Definition:
• Asthma is a heterogeneous disease, characterized by chronic airway inflammation in which
many cells and cellular elements play a role.
• Chronic inflammation causes diffuse, obstructive airway disease with:
- Hyper-responsiveness of the airways to a variety of stimuli
- High degree of reversibility of the obstructive process either spontaneously or with
treatment.
• Airway hyper-responsiveness and obstruction present as paroxysmal respiratory symptoms
such as wheeze, shortness of breath, chest tightness and/or cough that vary over time and
in intensity, together with reversible variable expiratory airflow limitation

Incidence:
• At least 10% in school children and much higher in the preschool age group
• Incidence before puberty: boys to girls is 2:1
• Thereafter, the sex incidence is equal

Age of onset:
• It occurs at any age; 30% are symptomatic by 1 year of age, 50% by 3 years and 80% have
their first symptoms before 5 years of age

Inheritance:
• It has a polygenic or multifactorial inheritance. A genetic predisposition combined with
environmental factors explains most cases of childhood asthma.

Pathophysiology
• Airway obstruction in asthma is due to
(1) bronchoconstriction
(2) hyper-secretion of mucus
(3) mucosal edema
(4) cellular infiltration with inflammatory cells and desquamation of bronchial epithelial cells
• Obstruction is most severe during expiration (airways normally are narrower in expiration)

105
• Airway obstruction leads to:
(1) Areas of hyperinflation
(2) Areas of segmental atelectasis
(3) Ventilation-perfusion mismatch
(4) Alveolar hypoventilation (leading to hypoxia, hypercarbia and acidosis)
• Asthma triggers: Various allergic and non-specific stimuli, in the presence of hyperreactive
airways, initiate bronchoconstriction and inflammatory response.

■---------------------------------------
Genetic predisposition
-------s
<_____________________
______________________
_______
■'
ZBronchial inflammation Symptoms
/-------------------------------- Airway narrowing
-
“ Oedema Bronchial
Reversible airflow Wheeze
Excessive mucus hyperresponsiveness
Atopy =£> obstruction T> Cough
production Infiltration with Exaggerated'twitchiness
k_______________________< (eg. peak Breathlessness
cells (eosinophils, mast " to inhaled stimuli
flow Chest
cells, neutrophils, _____________________ j
X lymphocytes) variability) tightness
_____)
.

A
Environmental trigger!

Upper respiratory tract infections

Allergens (e.g. house dust mite, grass pollens,
pets) Smoking (active or passive)
Cold air
Exercise
Emotional upset or anxiety
Chemical irritants (e g. paint, aerosols) y

____________________________________________
____________________________________________
____________________________________________
________________________________.

Asthma Triggers
- Allergens: e.g. house dust mite, pollens, pets, feathers, molds and food
- Viral respiratory infections: e.g. respiratory syncytial virus
- Cold air or exercise (exercise induced asthma)
- Emotional excitement and psychological stresses
- Drugs: e.g. aspirin and non-steroidal anti-inflammatory drugs
- Pollutants and tobacco smoke

On exposure to any of the above asthma triggers, mast cell degranulation and release of
chemical mediators occur. These mediators as well as cytokines released from blood cells
(eosinophils, basophils, lymphocytes and monocytes) are responsible for the inflammatory
changes that cause airway obstruction. Structural changes in the airways (airway wall
remodeling) occur in longstanding and severe inflammation.

106
Diagnosis of asthma:
❖ History
1. More than one symptom: wheeze, shortness of breath, cough, chest tightness
2. Symptoms are paroxysmal with symptom free intervals
3. Symptoms often worse at night or in the early morning
4. Symptoms vary over time and in intensity
5. Symptoms are triggered by viral infections (colds), exercise, allergen exposure, changes
in weather, laughter, or irritants such as car exhaust fumes, smoke or strong smell
6. Wheeze and distress precipitated by a trigger and relieved with bronchodilators.
7. History of other atopic manifestations in the child e.g. allergic rhinitis, skin, eye allergy,
family history of atopy.

❖ Physical examination:
No findings in symptom free intervals.
Prolonged expiration ± expiratory ronchi in symptomatic periods according to severity.
❖ Objective measurement of airflow obstruction (using peak expiratory flow meter
(PEFM) or spirometry pre and post bronchodilation)
❖ Assessment of atopy(skin prick tests, serum total or specific IgE)
❖ Others: chest X-ray, peripheral blood eosinophilia.

Differential diagnosis
Asthma should not be confused with other causes of wheezing and should never be
diagnosed on the basis of single wheezing episode

Common causes of chronic persistent or recurrent wheezing

- Bronchial asthma (the commonest cause of wheezing in children).
- Recurrent aspiration syndromes (e.g., gastroesophageal reflux, cerebral palsy, swallowing
disorders).
- Foreign body inhalation (sudden onset of persistent wheezing, no response to bronchodilators)
- Chronic or recurrent infections (e.g., cystic fibrosis, immunodeficiency, bronchopulmonary
dysplasia)
- Congenital anomalies or compression of the airways (e.g., cysts, laryngeal web, stenosis,
tracheoesphageal fistula, vascular ring, enlarged lymph nodes, tumors)
- Bronchiectasis
- Laryngotracheobronchomalacia
- Primary ciliary dyskinesia
- Congenital heart disease
- Chronic respiratory infection (e.g., TB)
- Vocal cord dysfunction

107
Diagnosis of asthma should include the following items:
1. Type of asthma (atopic, exercise induced etc)
2. Severity of asthma (as a chronic disease)
3. Degree of asthma control and risk of poor asthma outcome
4. Causes of acute attacks and their severity (identification of the triggering stimuli)

Periodic assessment of the child with

asthma
I: CBnical features to Monitor

check • Peak flow diary

• Severity and frequency of
—
Growth and nutrition symptoms
• Exercise tolerance
Peak flow/spirometry
_________________________________ • Interference with life, time off
_/ school
Chest for • Is sleep disturbed?
• Hyperinflation • Use of preventer and reliever
• Harrison's sulcus medication - are they
• Wheeze appropriate?
• Inhaler technique
• Lung function tests
Are there other allergic disorders?
Consider triggers:
• Allergic rhinitis
• Untreated allergic rhinitis
• Eczema
• Allergens or cigarette smoke
• Food allergy
v . • Stress

' X /------------------------------------------------\
If atypical features present Check:
• Sputum
• Finger dubbing ■ Child has an up to date personalized
• Growth failure asthma management action plan
- then seek another diagnosis
• Family have necessary medication/
< __________________________________________________
___________________________________________________ equipment to manage an acute
_'
exacerbation
k____________________________________
____________J

108
Classification according to asthma severity before starting treatment (Global
Initiative of Asthma Guidelines - GINA):
Classification based on symptoms and lung function before treatment.

Classification of Asthma Severity by Clinical Features Before Treatment

Intermittent
Symptoms less than once a week. Brief exacert ations
Nocturnal symptoms not more #ian twice a month.
• FEV, or PEF i 80% predicted
• PEF or FEV, variability < 20%

Mild Persistent
Symptoms more than once a week tut less than once a day. Exacerbations may affect actr.-ity and sleep. Nocturnal
symptoms more than t*ice a month.
• FEV, or PEF a 80% predicted
• PEF or FEV, variabilrty 20-30%

Moderate Persistent
Symptoms daiy. Exacerbations may affect activity arid sleep. Nocturnal symptoms more than once a week. Daily
use of inhaled short-acting p.-agonist
• FEV, or PEF 60 80% predicted
• PEF or FEV, variabilrty > 30%

Severe Persistent
Symptoms daiy. Frequent exacerbations. Frequent nocturnal asthma symptoms.
Limitation of physical activities
• FEV, or PEF s 60% predicted
• PEF or FEV, variabilrty > 30%

FEVi: forced expiratory volume in the first second. PEF: peak expiratory flow

109
Classification according to degree of asthma control
(Global Initiative of Asthma Guidelines - GINA): Assessment of asthma control
in children 5 years and younger:

A. Symptom
control
In the past 4 weeks, has the child had:
Well- Partly Uncontrolled
controlled controlled

• Daytime asthma symptoms for more than

few minutes, more than once/week? YesU NoU

• Any activity limitation due to asthma?

(runs/plays less than other children.
tires easily during walks/playing) YesQ NoU None of
• Reliever needed* more than once a these 1-2 of these 3-4 of these
week? YesU NoQ
• Any night waking or night coughing
due to asthma? YesO NoQ

B. Risk factors for poor asthma outcomes

ASSESS CHILD’S RISK FOR:
• Exacerbations within the next few months
• Fixed airflow limitation
• Medication side-effects

Assessment of asthma control in children 6-11 years:

The same as in children 5 years and younger with the exception of day time symptoms and
need for reliever medications more than twice a week.

110
 Management of Asthma
Objectives
1. Treatment of acute asthmatic attacks by asthma relievers.
2. Preventive treatment by prophylactic anti-asthma controllers.
3. Avoidance of the triggering stimuli.
4. Patient and family education.

A. Treatment of acute asthmatic attacks

Acute asthma attack is a flare-up or exacerbation leading to acute or sub-acute worsening

of symptoms and lung function compared with the patient’s usual status.
Severity of acute attacks:
Assessment of severity is very important for the clinical decision regarding the place of
management (home or hospital) and the lines of management

Clinical signs Mild Moderate Severe Life-threatening

Able to talk Able to talk in Cannot complete Able to pronounce a few
sentences sentences words

Respiratory rate" 1 Normal Increased Greatly increased Bradypnea/gasping

Heart rate b Normal Increased Greatly increased Fall in heart rate

Complexion Normal Pallor Pallor/cyanosis Cyanosis

Level of consciousness Normal Restlessness Severe restlessness Obtundation, drowsiness

Wheezing Mild expiratory Expiratory Expiratory/lnspiratory Silent chest

Absent Mild Moderate Paradoxical respiratory movement
Use of accessory muscles of
respiration
SpO2 >95% 92-95% <92% <90%

PaCO2 (mmHg) <38 38-42 >42 >42

Peak expiratory flow >80% 60-80% <60% Not measurable

Not all clinical signs are necessary to classify a given level of severity
'Normal values: at <2 months of age <60/min; at 2-12 months <50/min; at 1-5 years <40/min; at 6-9 years <30/min
'’Normal values: at 2-12 months of age <160/min; at 1-2 years <120/min; at 3-8 years, <110/min

Levels of severity of an asthma attack in

children

11
1
Goals and primary therapies for asthma exacerbations:
• Maintenance of adequate arterial oxygen saturation with supplemental oxygen.
• Relief of airflow obstruction with repetitive administration of rapid-acting inhaled
bronchodilators ([3-agonists alone or with anticholinergics).
• Reduction of airway inflammation with early administration of systemic corticosteroids
(CS).
• Closely monitor response to treatment with clinical assessment, serial measures of lung
function and pulse oximetry
• Doses, frequency and method of administration may vary according to severity and
response to treatment

Managing exacerbations in acute care settings

PEF s50% predicted or best

112
 Short-acting beta 2 -agonists Consider Short-acting beta 2 -agonists
ipratropium bromide Ipratropium bromide
Controlled 0 2 to maintain Controlled 0 2 to maintain saturation
saturation 93-95% (children 94-98%) 93-95% (children 94-98%)
Oral corticosteroids Oral or IV corticosteroids
Consider (V
magnesium
Consider high dose
ICS

I. II
If continuing deterioration, treat as severe
and re-assess for ICU

ASSESS CLINICAL PROGRESS

FREQUENTLY
MEASURE LUNG FUNCTION
in all patients one hour after initial treatment
I

f FEV. or PEF <60% of predicted or

FEV, or PEF 60-80% of predicted or personal
best and symptoms improved
> personal best,or lack of clinical
response
MODERATE
SEVERE
Consider for discharge
Continue treatment as above and
planning
reassess frequently

1
V/

Pressurized metered dose inhaler Dry powder inhaler 4 years and older Nebulizer: suitable for all ages
and spacer. Suitable for all ages.

113
Management of status asthmaticus (life threatening condition)
A. Hospitalization in ICU
B. Oxygen therapy (to correct hypoxemia)
C. I.V. fluid therapy (maintenance therapy)
D. Drug therapy
> Nebulized salbutamol: 0.25 - 0.5 ml added to 2-3 ml saline every 1-2 hours.
> I.V salbutamol: in ICU by infusion pump under continuous monitor.
> I.V methyl prednisolone 2mg/Kg first dose followed by 2mg/Kg/24h divided/6h or,
I.V. hydrocortisone: 5-10 mg/kg every 6 hours.
> I.V Magnesium sulphate 25-75mg/kg once slowly by infusion over 60 min.
> I.V. aminophylline: 5 mg/kg, slow I.V. every 6 hours (or 1 mg/kg/hour).

E. Mechanical ventilation: With marked CO2 retention (PaCO2 above 55 mm Hg), severe
hypoxemia, severe acidosis or disturbed consciousness.

B. Prophylactic anti-asthma controllers

The use of anti-inflammatory drugs (asthma controllers) is indicated in persistent
asthma. Inhaled corticosteroids and oral montelukast are the most effective.

Long term control medications for asthma

1. Inhaled glucocorticosteroids.
2. Leukotriene receptor antagonists - LTRA ( montelukast).
3. Long-acting inhaled ^-agonists - LABA (Salmeterol- Formeterol).
4. Long-acing theophylline.
5. Long-acting oral fh-agonists.
6. Systemic glucocorticosteroids.
7. Anti-lgE , anti-interleukin 5 (anti -IL5).
8. Long acting anticholenergic agents e.g. Tiotropium .
9. Cromones.

Immunotherapy is indicated in certain atopic patients with an evidence of specific IgE-

sensitization towards clinically relevant one (not more than three) relevent inhalant
allergen associated with consistent symptoms of allergic rhinitis/conjunctivitis and/or
allergic asthma. Immunotherapy should not be given to children less than 5 years of
age and should be given under the supervision of an allergist.

114
Stepwise approach to control the symptoms and minimize future risk in children
6-11 years and adolescents

•Not for children <12 years

••For children 6-11 years, the preferred Step 3 treatment is medium dose ICS
#For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy
t Tiotropium by mist inhaler is an add-on treatment for patients £12 years with a history of exacerbations

BDP/fbrmeterol: beclometasone/formoterol - BUD/formeterol: budesonide/fOrmoterol ICS: inhaled

corticosteroids; LABA: long acting belaz-agonist; med: medium dose; OCS: oral corticosteroids;
SLIT: sublingual immunotherapy.
• Provide guided self-management education (self-monitoring +written action
plan+ regular review)
• Consider stepping up if...uncontrolled symptoms, exacerbations or risks, but
Remember
check diagnosis, inhaler technique and adherence first
to:
• Consider stepping down if... symptoms controlled for 3 months + low risk for
exacerbations. Stopping ICS is not advised

115
 Stepwise approach to long term management of asthma in children
5 years and younger

STEP 4
PREFERRED STEP 3
CONTROLLER STEP 1 STEP 2 Continue
CHOICE
controller
Double & refer for
'low dose' specialist
Daily low dose ICS ICS assessment

Other
Leukotriene receptor antagonist (L TRA) Low dose ICS * L TRA Add LIRA
controller Intermittent ICS Inc ICS
options frequency
Add mfermtt ICS

RELIEVER
As-needed short-acting beta r agonist (all children)

CONSIDER THIS Infrequent Symptom pattern consistent with asthma {Asthma diagnosis, and not Not well-
viral wheezing and asthma symptoms not well-controlled, or iwell-controlled on low dose controlled on
STEP FOR
and no or *3 exacerbations per year |CS double ICS
CHILDREN WITH:
few interval Symptom pattern not consistent with asthma but wheezing
symptoms episodes occur frequently, e.g. every 6-8 weeks. First check diagnosis, inhaler skills, adherence,
Give diagnostic trial for 3 months. exposures

C. Avoidance of triggering factors:________________

- Avoidance of exposure to respiratory infections and common allergens is helpful in reducing
the number and severity of the acute attacks.
- Dust, cold air, smoke of cigarettes should be also avoided.
- The common trend of avoiding certain foods (as eggs, fish, chocolates etc.) in all asthmatic
patients should be avoided and kept for those with known allergy to certain foods.

D. Patient and family education:

• Children should not be exposed to environmental tobacco smoke during pregnancy or
after birth.
• Vaginal delivery should be encouraged where possible.
• Breast-feeding is advised.
• The use of broad-spectrum antibiotics during the first year of life should be discouraged.
• Care givers of asthmatic patients should be educated about:
- Nature of the disease and the prognosis.
- How to avoid the triggering stimuli.
- What to do in an acute attack.
- Correct use of inhalers and other delivery systems (as nebulizers).

116
 Allergic Rhinitis and Conjunctivitis
Incidence
- Underestimated
- Affecting up to 20% of children and can severely disrupt their lives

Etiology
A. Seasonal allergic rhinitis is predominantly due to sensitization and exposure to airborne
pollens and spores

B. Perennial allergic rhinitis is usually due to sensitization and exposure to house dust mite
or pets

Presentation
• Classic presentation of coryza, conjunctivitis, sneezing and itching of nose
• Can also present as 'cough-variant rhinitis' due to post-nasal drip and may be detrimental to
concentration
• It is associated with eczema, asthma, sinusitis and adenoidal hypertrophy.
• Treatment of allergic rhinitis has been shown to improve coexistent asthma

Treatment
• Antihistamines 2 nd generation non-sedating antihistamines (topical or systemic)
• Topical corticosteroid nasal sprays.
• Cromoglycate eye drops
• Leukotriene receptor antagonists, e.g., monteleukast
• Nasal decongestants (use for no more than 7-10 days due to risk of rebound effect)
• Allergen immunotherapy
• Systemic corticosteroids should NOT be used due to the risk of adverse effects

117
 Food Allergy and Food Hypersensitivity
Incidence
- Rare, affecting 6 to 8 % of children

Mechanism
- Immune response against a specific food protein
- IgE mediated or non-lgE mediated
- Even a tiny amount of the allergy-causing food can trigger signs and symptoms

Presentation
• Onset of symptoms: few minutes to 2 hours after eating the offending food
• It can occur even after the first time of ingestion of a food
• Tingling or itching in the mouth
• Hives, itching or eczema
• Swelling of the lips, face, tongue and throat, or other parts of the body
• Wheezing, nasal congestion or trouble breathing
• Abdominal pain, diarrhea, nausea or vomiting
• Dizziness, lightheadedness or fainting
• Anaphylaxis with life-threatening symptoms: Emergency treatment is critical
• Untreated anaphylaxis can cause coma or death
• In infants the most common causes are milk, egg and peanut
• In older children peanut, tree nut and fish
• While there is no cure, some children outgrow their food allergy as they get older

Important Remarks
- Food intolerance: less serious condition that does not involve the immune system
- Food aversion: Refusal of food for psychological or behavioral reasons
- Food-associated exercise-induced anaphylaxis: a disorder in which exercise is tolerated
and food is tolerated, but when exercise follows ingestion of a specific food, anaphylaxis
results

Diagnosis
- Typical history of exposure
- Gold standard: Double-blind placebo-controlled food challenge. Administration of
increasing amounts of the food, starting with a tiny quantity until a full portion is reached.
The test should be performed in hospital (close monitoring)
- Skin prick tests
- Measurement of specific IgE antibodies in blood

Treatment
- Avoidance of food of exposure (very difficult for milk & nuts)
- The advice of a pediatric dietician is essential
- Mild reactions: Antihistaminics
- Severe reactions: IM epinephrine (adrenaline)

118
 Atopic Dermatitis (Atopic Eczema)
Incidence
- Very common, affecting 10 % of children
Mechanism
- Allergic reaction (raised IgE level)
- Up to 50% of affected children develop other allergic diseases

Presentation Eczema has been called "the itch

• Onset: Almost always before 5 years of age that rashes" because the itching
• All ages can be affected usually occurs first
• Description of the lesions:
- Itchy, dry, red skin and small bumps on cheeks, forehead, or scalp
- The rash may spread to the extremities and the trunk
- Some children develop circular, slightly raised, itchy, and scaly rashes in the bends of
the elbows, behind the knees, or on the backs of the wrists and ankles
- As kids get older, the rash is usually less oozy and scalier

Diagnosis
- Children with eczema may have food allergy (e.g., cow's milk allergy) and exposure to the
offending food can worsen the disease
- If the eczema is severe and a food allergy is suspected: food elimination diet
- Food challenge can be performed

119
Treatment

The goals for the treatment are to prevent itching and inflammation Treatment may
involve both lifestyle changes and medications Treatment is always based upon an
individual's age, overall health status, and the type and severity of the condition

- Avoid frequent hot baths (which tend to dry the skin)

- Use warm water with mild soaps or nonsoap cleansers
- Avoid excessive scrubbing after bathing.
- Avoid dressing the child in harsh or irritating clothing
- Use soft clothes that "breathe," such as those made from cotton
- Apply moisturizing ointments (such as petroleum jelly), lotions, or creams to the skin
regularly and always within a few minutes of bathing, after a very light towel dry
- Apply cool compresses (such as a wet, cool washcloth) on the irritated areas of skin
- Keep the child's fingernails short to minimize any skin damage caused by scratching
- Avoid becoming overheated, which can lead to flare-ups.
- Eliminate any known allergens such as certain foods, dust, or pet dander
- Drink plenty of water, which adds moisture to the skin
- Corticosteroid creams are sometimes prescribed to decrease the inflammatory reaction in
the skin. Use mild-, medium-, or high-potency corticosteroid creams according to the
severity of the symptoms
- If itching is severe, oral antihistamines may be prescribed.
- In some cases, a short course of oral corticosteroids (such as prednisone) is prescribed,
although their long-term use is discouraged in the treatment of this nonlife-threatening
condition because of unpleasant and potentially harmful side effects

Drug Allergy
Incidence
- Drug allergies do occur in children, especially to antibiotics
- Only a minority who are labelled drug allergic are truly allergic as viral illnesses, for which
children are often prescribed antibiotics, themselves cause skin rashes

Diagnosis
- Detailed history of the nature and timing of the rash in relation to drug intake
- Allergy, skin and blood tests are unreliable in predicting drug allergy
- Drug challenge is the only way to confirm the diagnosis

120
 Urticaria
Classification and Mechanism
A. Acute urticaria
- Usually results from exposure to an allergen or a viral infection, which triggers an
urticarial skin reaction
- It may also involve deeper tissues to produce swelling of the lips and soft tissues
around the eyes (angioedema), and even anaphylaxis

B. Chronic urticaria (persisting >6 weeks)

- It is usually non-allergic in origin
- Results from a local increase in the permeability of capillaries and venules
- Activation of skin mast cells with release of mediators including histamine
- A cause may be identified (such as cow's milk allergy) in infants
- But most cases are idiopathic

Etiology
1. Idiopathic (Common)
2. Infection
3. IgE-mediated
o Specific food: cow's milk, nuts (especially peanuts), fish
o Blood products
o Drugs: penicillins, cephalosporins
4. Pharmacological
o Foods containing histamine-releasing substances, e.g. strawberries, egg, white,
cheese
o Aspirin and other non-steroidal anti-inflammatory agents
5. Physical: heat, cold, pressure

121
 Sting Hypersensitivity (Insect bite)
Etiology
- Mainly bee and wasp stings
- Fire ants in the USA, Asia and Australia

Presentation
• Mild: local swelling
• Moderate: generalized urticaria
• Severe: systemic symptoms with wheeze or shock.

Treatment
- Children with a previous mild or moderate reaction are unlikely to develop a severe
reaction in the future and the families can be reassured
- Those who had a severe reaction should carry an epinephrine (adrenaline) auto¬
injector and be desensitized using specific immunotherapy

122
 Investigations of Liver Diseases

Laboratory
1. Liver Function Tests:
a. Total and direct serum bilirubin
b. Alanine aminotransferase (ALT), aspartate aminotransferase (AST)
c. Alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT)
d. Serum albumin, prothrombin time (PT) and international normalized ratio (INR)
2. Hepatitis markers: See later
3. Test for Metabolic diseases:
a. Enzyme assay as in Gaucher disease, Niemann-Pick disease, GSD
b. Galactose 1 phosphate uridyl transferase assay in galactosemia
c. Ceruloplasmin level in Wilson disease
d. Alpha 1 antitrypsin in alpha 1 antitrypsin deficiency

Imaging
1. Abdominal Ultrasonography for diagnosis of:
a. Hepatomegaly, hepatic echogenicity, focal lesions
b. Splenomegaly & ascites
2. Doppler, MRA and MRV (Magnetic Resonance Venography) for assessment of:
a. Portal and splenic veins
b. Hepatic artery and hepatic veins

Invasive
1. Upper GIT endoscopy: for esophageal
varies
2. Liver biopsy: very helpful in the diagnosis

123
 Viral Hepatitis

Hepatotropic viruses: A, B, C, D, and E

HAV HBV HCV HDV HEV

Type of virus Enterovirus Hepadnavirus Flavivirus Incomplete Calcivirus

(RNA) (DNA) (RNA) (RNA) (RNA)
Transmission Feco-oral Parenteral, Parenteral, Parenteral, Feco-oral
routes sexual, vertical sexual, vertical sexual, vertical

Incubation 2-6 weeks 2-6 months 1-5 months 3-6 weeks 2-9 weeks
period
Diagnostic test Anti-HAV HBsAg, anti- Anti-HCV Anti-HDV Anti-HEV
igM HBcIgM HCV-RNA by
PCR
Vaccine Yes Yes No Yes (HBV) No

Chronicity No Yes Yes Yes No

Fulminant Rare Yes Rare Yes Yes

disease

Other viruses: cause systemic manifestations that sometimes affect the liver
a. Epstein-Barr virus: in 40 % of cases, less than 5% become jaundiced
b. Cytomegalovirus
c. Herpes simplex virus.

Hepatitis D RNA

Hepatitis B
surface antiaen

Hepatitis
D
Antigen
DNA

124
Clinical types of acute hepatitis: of 4 clinical types

1. Icteric hepatitis: it is the commonest form(3 stages)

a. Pre-icteric stage: 4-6 days
• Fever, anorexia, headache and malaise.
• Abdominal pain and vomiting.
• Urine usually becomes dark(bilirubinemia) during the last 1-3 days

b. Icteric stage: 2-4 weeks

• Jaundice, dark urine and clay colored stool.
Liver is enlarged and tender.
• The early manifestations as fever, vomiting disappear but anorexia may continue

c. Convalescence stage :gradual decline of jaundice and decrease in liver size

Dark Jaundic Enlarged tender

urine e liver
2. Cholestatic hepatitis
■ Marked obstruction of biliary flow ->
■ Pruritus (bile acids) and marked clay colored stool.

3. Anicteric hepatitis
■ Commoner in infancy.
■ Jaundice is absent, presentations include: anorexia, vomiting, diarrhea and colic

4. Fulminant hepatitis: see later

Acute liver failure (the least common but the most serious: 70% mortality)

125
Diagnostic investigations of acute hepatitis)

To diagnose liver cell injury

To diagnose acute liver cell failure

To diagnose the causative virus

To diagnose liver cell injury

1. Bilirubin: direct or mixed hyperbilirubinemia.

2. AST (aspartate aminotransferase) and ALT (alanine aminotransferase) are elevated (10
folds).
3. Urine analysis: bilirubin is present.

To diagnose acute hepatic failure

1. Raising Bilirubin level (above 10 mg/dl, level above 20 mg/dl may also occur).
2. Liver transaminases (ALT, AST) are increased (10 -100 times normal).
3. Low serum albumin (below 3 gm/dl occurs later because of long half-life of albumin)
4. INR (international normalized ratio) >2, uncorrectable with vitamin K or INR between 1.5
and 1.9 uncorrectable with vitamin K plus encephalopathy.
5. High blood ammonia level
6. Metabolic Acidosis.
7. Hypoglycemia, Hypokalemia and Hyponatremia.

To diagnose the causative virus (hepatitis marker)

1. Hepatitis A
• IgM antibodies to hepatitis A (anti HAV IgM): recent infection(acute disease).
• IgG anti HAV antibodies persist after recovery (immunity).
2. Hepatitis B
• HBsAg (surface antigen) followed by anti HBc (core antibodies) IgM: indicate recent
infection.
• Anti-HBs (surface antibodies) appear after recovery and indicate immunity.
• Persistence of HBsAg (surface antigen) and anti HBc IgG indicate chronicity.

3. Hepatitis C
• Anti-HCV antibodies: these antibodies denote exposure to infection but do not mean
recovery or development of immunity.
• HCV- RNA antigen detected by PCR (polymerase chain reaction) denotes viremia

126
 Viral load can be assessed by quantitative PCR for treatment purposes

4. Hepatitis D, and E
• Anti-HDV and anti HEV antibodies (IgM).
• Hepatitis D virus antigen

General measures
1. HAV
• Isolation of acute cases for 7 days after onset of jaundice (infectivity period).
■ Strict hand washing, especially after changing diapers and before preparation or serving
food.
2. HBV , HCV, and HDV
• Strict screening of blood and blood products.
• Strict sterilization for all procedures in which there is contact with blood
• Prevention of perinatal transmission during delivery of infected mothers
Vaccination
1. HAV : A potent inactivated hepatitis A vaccine is available (Non-compulsory)
2. HBV
■ Hepatitis B vaccine was included in vaccination program in Egypt since 1993
■ Routine vaccination of all newborns (1st dose is recommended at birth)
• Vaccination should also target high risk groups:
e.g.. thalassemics and hemophilics receiving repeated blood and blood products.
• Patients with chronic liver disease must also be protected from superadded hepatitis
A or B infections.
3. HCV: No available vaccine.
4. HDV : vaccination against hepatitis B

127
Acute liver cell failure: acute fulminant
hepatitis
Definition
Sudden failure of the liver to perform its functions, namely the metabolic, excretory and
detoxifying functions.
It is very serious with bad prognosis and high mortality

Etiology
1. Infections: Viral hepatitis: Hepatitis A, B, D, others, EBV, CMV
2. Metabolic: Wilson's disease, Tyrosinemia
3. Toxins I Drugs: Paracetamol, NSAID, Erythromycin, isoniazid, Halothane
4. Autoimmune: Autoimmune hepatitis
5. Reye syndrome: Aspirin + Varicella or influenza

Pathophysiology and clinical picture

Pathophysiology Clinical picture

Disturbance of hepatic metabolic functions

1. Coagulopathy ( decreased synthesis of coagulation Bleeding tendency mainly GIT( stress
factors)
ulcers) and easy bruising Hepatic
2. Retention of some amino acids and same short
encephalopathy
chain fatty acids
3. Neutrophilic dysfunction Secondary bacterial infection(sepsis)
■^systems failure^ respiratory failure

4. Hypoalbuminemia Fluid retention and ascites

5. Electrolyte disturbances : hyponatremia,

hypokalemia and hypoglycemia
Disturbance of hepatic excretory functions
1. Elevated serum bilirubin except in Reye $

2. Elevated serum bile salts Progressive jaundice except in

Reye$
Renal failure (hepatorenal syndrome)
Disturbance of hepatic detoxifying functions
1. Elevated ammonia level

Persistent vomiting
Brain edema^Hepatic encephalopathy
Brain edema may be also due to cerebral
vasodilatation, hyponatremia and
hypoalbuminemia

128
Investigations :( see investigations of fulminant hepatitis)

Management

Close monitoring
1. Clinical monitoring
• Vital signs
Level of consciousness
• Urine output, edema and ascites
• Signs of brain edema, bleeding and evidence of infections
2. Laboratory monitoring
• Liver functions, prothrombin time kidney functions
• Blood ammonia, blood sugar, serum electrolytes

Conservative measures
1. Correction of water, electrolytes imbalance and feeding
• IV fluids: fluid restriction to 60-70% + diuretics
• IV salt free albumin
• Feeding oral, nasogastric or total parenteral nutrition
2. Reduction of ammonia level :reduce protein intake, Neomycin and Lactulose (oral or
enema)
3. Control of bleeding: fresh frozen plasma or fresh whole blood, IV vitamin K and antacids
4. Control of infections: antibiotics guided by cultures and consider hepatic toxicity
5. Control of fluid retention and ascites: fluid restriction ± diuretics
6. Brain edema: head elevation, IV drip Mannitol and therapeutic hyperventilation

Drastic measures
1. Charcoal hemoperfusion
2. Liver transplantation

129
 Chronic Hepatitis

Definition
Continuing inflammatory disease of the liver for more than 6 months with the potential to
either:-
1. Progress to more severe disease including cirrhosis
2. Continue unchanged
3. Subside with or without treatment

Etiology = causes of liver cirrhosis

1. Chronic viral hepatitis(B, C,D ) : (A and E do not cause chronic liver disease)
2. Autoimmune chronic hepatitis.
3. Drug induced (INH, Rifampicin).
4. Metabolic disease: Wilson disease , alpha 1 antitrypsin
5. Chronic inflammatory bowel disease e.g. ulcerative colitis.
6. Nonalcoholic fatty liver disease
Incidence: Most common cause in developed countries
Presentation: Obese children: lethargy and right upper quadrant pain
The most common causes are post viral hepatitis (B, C, D) followed by autoimmune
hepatitis

Clinical picture
1. Acute hepatitis which fails to resolve within 6 months
2. Insidiously diagnosed in an asymptomatic child or present with
■ Firm hepatomegaly
■ Hepatosplenomegaly
* Manifestations of chronic liver cell failure:

Jaundice - bleeding - Ascites - spider naevi - palmer erythema

3. Other symptoms of the cause

■ Corneal findings (kayser-Fleischer ring) in Wilson
■ Skin rash, arthritis and hemolytic anemia in autoimmune hepatitis
■ GIT manifestation in ulcerative colitis
Complications

130
1. Cirrhosis and hepatocellular carcinoma especially with chronic HBV and HCV infection.
2. Portal hypertension (Varices, ascites).
3. Liver cell failure growth failure and hepatic encephalopathy

Chroni
c

Portal
hypertension
Investigations

A. Investigations to assess liver functions: liver function tests are usually abnormal
1. Bilirubin level, total and direct.
2. Enzymes: ALT, AST and alkaline phosphatase.
3. Alkaline phosphatase and gamma glutamyl transpeptidase.
4. Plasma proteins.
5. INR

B. Investigations to search for the etiology

1. Laboratory
a. In post viral chronic hepatitis: Hepatitis markers e.g. persistence of HBsAg.
b. In autoimmune hepatitis
• Hypergammaglobulinaemia.
• Positive autoantibodies, e.g. anti-smooth muscle antibodies, anti-nuclear DNA
antibodies or liver/kidney microsomal antibodies.
c. Wilson disease
• Low serum ceruloplasmin, low serum copper.
• Kayser-Fleischer rings by slit lamp examination, (copper accumulation in the
cornea)
2. Imaging:

131
 a. Ultrasound: to assess liver texture, portal vain caliber, spleen size and the presence
of ascites
b. Doppler: to assess portal vein patency, direction of blood flow and the presence of
porto systemic anastomosis
3. Endoscopy: upper GIT Endoscopy may show esophageal varices.

4. Study of ascitic fluid tap

5. Liver biopsy assesses the grade of inflammation and stage of fibrosis

Varice
s

Treatment

Treatment of any correctable condition

1. Post viral: oral Antiviral drugs e.g. ribavirin and long acting interferon
2. Autoimmune hepatitis prednisolone and azathioprine.
3. Wilson disease: Penicillamine is a copper chelating agent (promotes urinary copper
excretion)

Liver supportive measures

1. Nutritional support
• Vitamin, minerals and carbohydrate rich diet.
■ Fat in the form of medium chain triglycerides.
2. Ascites
• Sodium and fluid restriction and diuretics.
• Albumin infusions or Paracentesis for refractory ascites
3. Encephalopathy
■ Treat precipitating factors e.g. GIT bleeding
• Protein restriction
• Oral lactulose to reduce ammonia reabsorption (it lower colonic pH and increase
colonic transit)

Liver transplantation in end stage liver disease: survival rate 70-90%

Started in Egypt in 2001

132
 Neonatal Cholestasis

Definition
Failure of normal amount of bile to reach duodenum due to liver or biliary cause.
There is elevation of direct (conjugated) bilirubin more than 20 % of the total bilirubin,
together with cholesterol and bile acids.

Etiology
1- Idiopathic neonatal hepatitis (giant cell hepatitis): The most common
cause- associated with IUGR
2- Infections:
a. Bacterial: neonatal sepsis, urinary tract infection
b. Viral: CMV, Rubella

c. Protozoal: toxoplasma ______

3. Metabolic:
a. CHO metabolism: Galactosemia
b. Amino acid metabolism: Tyrosinemia
c. Lipid storage disease: Niemann-Pick disease ■
d. Alpha-1- antitrypsin deficiency

e. Bile acid biosynthetic defects

Paucity of intrahepatic bile

4- Familial cholestatic syndromes:

a. Paucity of intrahepatic bile ducts
b. Alagille syndrome:
■ Paucity of intrahepatic bile ducts
■ Associated with congenital heart disease, vertebral anomalies

■ Cornea anomalies and triangular

face
c. Progressive familial intrahepatic cholestasis (PFIC): Types 1, 2 and 3
d. Benign recurrent cholestasis

5- Extrahepatic biliary atresia (EHBA)

The 2 nd most common cause
(Associated with normal birth weight)

6- Choledochal cyst

133
Consequences of cholestasis
1. Decreased bile delivered to the intestine:
a. Fat malabsorption
b. Fat soluble vitamin deficiencies (A, D, E, K)
c. Pale or clay colored stool
2. Retention of bile constituents:
a. Jaundice
b. Pruritus (retained bile acids)
c. Progressive liver damage

Clinical manifestations

1. Cholestasis should be suspected in any case of persistent neonatal jaundice

beyond 2 weeks
2. Picture of cholestasis (consequence)
3. Manifestations of specific cause:
a. Marked hepatomegaly with adequate growth: suspect extrahepatic biliary atresia
b. Low birth weight, microcephaly and hepatosplenomegaly: suspect congenital
infection
c. Cataract: Galactosemia or congenital rubella
d. Abnormal facies, congenital heart disease and vertebral anomalies: suspect Alagille
syndrome
4. Picture of complications:
a. Failure to thrive
b. Cirrhosis in infancy
c. Portal hypertension and splenomegaly
d. Liver cell failure

134
Investigations: laboratory approach for cholestasis

In spite of multiplicity of the conditions causing neonatal cholestasis, most cases are caused by
idiopathic hepatitis and biliary atresia.
Early differentiation between these 2 conditions is important because in case of biliary atresia,
early surgical correction will prevent further hepatic injury

Investigations to diagnose cholestasis

1. Increased total and direct bilirubin ( direct bilirubin > 20% of total bilirubin)
2. Increased AST (aspartate transferase) and ALT (alanine transferase)
3. Increased alkaline phosphatase and Gamma Glutamyl Transpeptidase (GGT is normal in
progressive familial intrahepatic cholestasis and bile acid synthesis defects)

Investigations to determine the cause (5 steps):-

1. Search for treatable cause

■ Galactosemia: reducing substance in urine or Galactose lphosphate in blood while the
infant is receiving a lactose containing formula.
Measuring the enzyme galactose-l-phosphate-uridyl transferase in red cells.
• Septicemia and other bacterial infections: CBC, CRP, ESR, cultures.

2. Search for TORCH infections

■ Total IgM antibody: level above 18-20mg/dl is highly suggestive.
■ Specific antibodies of TORCH agents e.g. CMV

3. Search for metabolic conditions

• dj antitrypsin assay (oijantitrypsin deficiency): normal serum level 150-250mg/dl
• Tyrosinemia: -> succinyl acetone in urine and aminogram.

4. Exclude choledochal cyst: By abdominal ultrasonography.

5. Differentiation between neonatal hepatitis and extrahepatic biliary atresia
• Liver scan ( HIDA)
• In extra hepatic biliary atresia: no excretion of dye in the intestine.
• In hepatitis excretion of dye in the intestine can occur.
■ Liver biopsy : the most important
• In neonatal hepatitis: giant cell transformation and degeneration of hepatocyte.
• In atresia: expansion of portal areas with fibrosis and bile duct proliferation.

135
Treatment

A. Extra hepatic biliary atresia: early diagnosis is very important

1. Correctable lesion (rare): direct drainage.
2. Non correctable lesion: Kasai operation, it must be done before 60 days to obtain best
results.
3. Liver transplantation for end stage liver disease
Biliary atresia is the commonest indication for liver transplantation in infancy.

B. Treatment of correctable conditions.

1. Antibiotics for septicemia or urinary tract infections
2. Elimination of lactose from diet in Galactosemia.
3. Surgical treatment of choledochal cyst

C. Liver supportive measures:

1. Replacement therapy
• Fat soluble vitamins
■ Fat in the form of medium chain triglycerides
■ Predigested formula

2. Symptomatic:
■ Pruritis: bile acid binders as cholestyramine
■ Varices: injection sclerotherapy or band ligation
■ Hepatic encephalopathy: 10% glucose infusion, enema and oral neomycin

D. Liver transplantation: most common indication in infancy, especially in EHBA

Stomach

Duode Small
ni intestine
Connected to
liver

Kasai operation:
Hepatoportoenterostomy

136
 Portal Hypertension

Definition
Increased pressure in the portal circulation above 10-12 mmHg (Normal: 5-10 mmHg)

liver

inferior

pancrea mesenteric vein

s
sup*nor
mesenteric vein

Etiology
1. Pre-hepatic
■ Portal vein thrombosis due to
o Umbilical sepsis
Omphalitis-> thrombophlebitis of the umbilical vein
is the most common
o Umbilical vein catheterization.
■ Congenital portal vein obstruction

2. Hepatic
• Presinusoidal: causes in the portal tracts
• Congenital hepatic fibrosis and bilharziasis
■ Sinusoidal
Causes of liver cirrhosis and cholestasis
• Post sinusoidal: central vein thrombosis
• VOD (veno-occlusive disease)

3. Post hepatic
• Budd-Chiari syndrome
■ Constrictive pericarditis

137
Pathophysiology
1. Congestion of abdominal viscera drained by portal vein: splenomegaly
2. Development of porto-systemic collaterals
a. Esophageal varices
b. Anorectal varices (Piles)
c. Caput medusa: Dilated veins around the umbilicus

Clinical presentation of portal hypertension

1. Hematemesis from esophageal Varices (may be the first presenting symptom)
2. Abdominal examination
a. Dilated abdominal wall veins (Caput medusa :site of porto systemic anastomosis)
b. Ascites; become evident with advanced cases (due to hypoalbuminemia, sodium
retention).It occurs early in post sinusoidal portal hypertension
c. Organomegaly
Pre hepatic: significant early splenomegaly with normal liver (hypersplenism may occur
resulting in pancytopenia.
Hepatic: mild to moderate splenomegaly, liver enlarged or shrunken according to the
disease
Post hepatic: liver: marked hepatomegaly, normal spleen

Il u

Ascites and Organomegaly Bleeding oesophageal Varices

Investigations
1. Upper GIT endoscopy: detect esophageal varices
2. Abdominal ultrasonography and Doppler:
■ Direction of flow within the portal system
■ Patency of the portal vein and
■ Presence of portosystemic collaterals.
3. CT angiography and MR venography (demonstrate vessel patency)
4. Liver function test
5. Investigation for the cause:
Hepatitis markers, autoimmune screening, sweet chloride test, liver biops

138
Prevention and management of variceal hemorrhage

Management of variceal hemorrhage

1. Emergency therapy for bleeding varices - .
• Hospitalization: Anti-shock measures: blood transfusion, intravenous fluids.
• Correction of coagulopathy: vitamin k, fresh plasma, platelets transfusion.
• Nasogastric tube placement.
• H2 receptor blocker (ranitidine) IV to decrease risk of bleeding from gastric erosion
• Vasopressin infusion if bleeding persists.
2. Emergency endoscopy (if hemodynamically stable): and either injection sclerotherapy or
band ligation.
3. Emergency shunt:
Trans jugular intrahepatic Porto-systemic shunt (TIPSS)
Surgical Porto-systemic shunts

Prevention of bleeding from varices

1. Prevention of the first attack of bleeding

• Avoid aspirin and non-steroidal anti-inflammatory drugs.
’ B adrenergic blockers (Propranolol) to lower the pressure in portal area.
• Prophylactic sclerotherapy or band ligation.
Prevention of re-bleeding; in addition to the above, the following may needed:
2.
• Beta adrenergic blockers (propranolol)
• Endoscopic sclerotherapy or band ligation
• Surgical porto-systemic shunt
• Liver transplantation

Banded varices
Esophagus A Rubber Band

Injection sclerotherapy Rubber band ligation system

Liver cirrhosis

Definition: Irreversible damage of liver architecture with fibrosis and nodule formation.

139
Causes
1- Causes of chronic hepatitis
2- Biliary cirrhosis (causes of cholestasis)
3- Congestive: Constrictive pericarditis and Budd Chiari syndrome

Causes of hepatomegal

Storage
1. Fat: malnutrition, obesity, cystic fibrosis, metabolic liver disease
2. Specific lipid storage diseases: Niemann-Pick & Gaucher disease
3. Glycogen: glycogen storage diseases, infant of diabetic mother
4. others: Alpha-l-antitrypsin deficiency, Wilson disease, Schistosomiasis

Inflammation
1. Acute and chronic viral hepatitis
2. Liver abscess
3. Autoimmune hepatitis

Infiltration
1. Cystic: choledochal cyst
2. Malignant: hepatoblastoma, hepatocellular carcinoma
3. Metastases: neuroblastoma, histiocytosis, leukemia, lymphoma

Increased vascular resistance

1. Budd-Chiari syndrome
2. Hepatic veno-occlusive disease
3. Right-sided heart failure
4. Constrictive pericarditis
5. Restrictive cardiomyopathy

Increased biliary spaces

1. Biliary obstruction: biliary atresia
2. Congenital hepatic fibrosis

140
 Hypothyroidism

Thyroid hormones Synthesis

Bindi
• Iodide is ng • 2(di-iodotyrosin)=T4
taken by the • l(di-iodotyrosin) +
• I + tyrosin=
gland and monoiodotyrosin=T3
Monoiodotyrossin
converted to • l+l+tyrosin= Dl-
iodine (I) iodotyrosin
Coupling t
Trappi V____—_____/
ng
The majority of T3 is synthesized fromT4 by peripheral
deiodenation

Thyroid hormone regulation

Hypothalamu<

HMMiVf
Thyrotropin-releating
hormone (TRH)
Stimulates(pituitary
to release TSH

Pituitary

Thyroid - stimulating
----- hormone (thyrotropin)
Stimulates thyroid gland
to release thyroid
hormone

Thyroid gland

deiodmase
T3 ---

Thyroid hormones actions

1. Growth and development (Brain : neurogenesis and myelination), deficiency in early life irreversible
->brain damage and mental retardation
2. Metabolism: stimulate oxygen consumption.
3. C.v.S: stimulate cardiac functions.
4. G.I.T.: stimulate motility.
5. Blood: synthesis of RBCs.
6. Transform carotene -> Vitamin A

141
 thyroidis
mtime of onset
1. According to the
• Congenital hypothyroidism: presents early in neonatal period and early infancy
• Acquired hypothyroidism: presents in childhood after a period of normal growth

2. According to the site of lesion

Primary hypothyroidism: thyroid gland lesion (which may be congenital or
acquired): T3 (Triiodothyronine) and T4 (Tertraiodothyronine) are low while TSH is high.
Secondary hypothyroidism: pituitary or hypothalamic lesion: low TSH, T4 and T3

Etiology of hypothyroidism (primary and

seconds
1. Primary hypothyroidism (congenital and acquired)
■ Congenital hypothyroidism
It is more serious because it affects the developing brain, early detection by neonatal thyroid
screening is important to prevent mental retardation.
a) Maldevelopment and mal-descent of thyroid gland (nongoitrous)
■ Agenesis (aplasia) is the most common
■ Dysgenesis (hypoplasia) the gland is present but small and underdeveloped.
■ Ectopic thyroid: the gland is usually dysgenetic and located anywhere between the root
of the tongue and suprasternal notch
b) Dysmorphogenesislgoitrous)
Autosomal recessive inborn error of hormonal synthesis

c) Iodine deficiency (endemic goiter): in Sinai and Oasis

d Antenatal maternal intake of ins: antithyroid drugs (e.g. thiouracil or
) radioactiv
e iodine).

• Acquired hypothyroidism
Hashimoto thyroiditis: autoimmune disease of the thyroid gland that may be associated with
other autoimmune disorders e.g. type 1 diabetes

2. Secondary hypothyroidism
• Isolated TSH deficiency is rare (less thanl% of cases) and is usually associated with pituitary
dysfunction.
• It is usually manifests with:- Growth hormone, gonadotrophin and adrenocorticotrophic
hormone (ACTH) deficiencies leading to hypoglycemia or micropenis and undescended testes
in affected boys before hypothyroidism become evident

142
Clinical picture of congenital hypothyroidism

Neonatal period
No specific manifestations so screening is essential for diagnosis and prevention of
mental retardation

■ At birth: no symptoms due to Trans placental passage of maternal T4 (thyroxin).

■ Later on: early weeks of life
History
1. Prolonged gestation period may be noticed
2. Prolonged jaundice.
3. Poor feeding
4. Crying is little with much sleep (decreased activity)
5. Constipation

Examination
1. Fontanels: Widely opened anterior and posterior fontanels
2. Failure to thrive
3. Hypothermia (cold, mottled skin) and slow pulse
4. Hypotonia: abdominal distention and umbilical hernia

In older infants and children: late manifestations

1. Motor retardation: delayed sitting, standing and walking.

2. Mental retardation: delayed mother recognition and speech development.
3. Physical retardation in neglected cases: Short stature with inappropriate upper segment/
lower segment ratio, body retains infantile proportion 1.7/1 (the limbs are short because
thyroxin is necessary for growth of long bones).
4. Coarse features
• Head: widely opened anterior fontanels.
■ Hair
• Coarse and brittle
• Low anterior hairline.
■ Forehead: short and wrinkled.

143
 ■ Eyelids swollen
• Mouth
• Mouth is kept open
• Large protruded tongue.
• Lips: pallor.
• Delayed dentition.
• Skin : pallor, dray and yellow (hypercarotenemia
■ Neck
• Short and thick
Goiter may be present
■ Trunk
• Distended abdomen and umbilical hernia.
■ Limbs
• Short limbs.
• Hands: broad and short

Clinical picture of acquired hypothyroidism

It is more prevalent in females
■ Physical: Short stature/poor growth
■ Mental: Deterioration in school work and learning difficulties
■ Sexual: Delayed puberty and amenorrhea
■ Metabolic: Cold intolerance
■ GIT: Constipation
■ Cardiac: Bradycardia
• Others
• Pallor, dry skin and thin dry hair
• Puffy eyes with loss of eyebrows
• Goitre, Obesity
• Slow-relaxing reflexes

Investigations of hypothyroidism

Laboratory: Thyroid profile: T3, T4, And T.S.H.

1. LowT4 (normal range 5-12 microgram/dl).
2. High TSH (normal: 0.5 - 4 micro unite/L). TSH is markedly elevated (above 50 micro unite/L).
It is the most sensitive test for primary hypothyroidism.

Imaging
1. Plain X ray: delayed bone age. it is characteristic for congenital hypothyroidism
2. Thyroid scanning (radioactive iodine : I 123) it is essential for diagnosis of the cause (it can
differentiate between aplasia, ectopic dysplasia, and malfunction of the thyroid gland)
3. Thyroid Ultrasonography

144
Neonatal thyroid screening
It is implemented in Egypt for all newborns to prevent mental retardation.
1. Timing: between 3nd and 7 th day of life.
2. Technique: a blood drop is obtained by heel prick on filter paper and analyzed for TSH.
3. Interpretation: if TSH level > 20 mil/ L, an immediate blood sample is withdrawn and
analyzed. If data are confirmed treatment is immediately initiated.

Thyroid agenesis Absence of ossific centers

Normal scan

Heel prick test: neonatal thyroid screening

Treatment

Lifelong therapy with L thyroxin to maintain normal growth,T3 and T4

1. Onset: should be started before 2 weeks to 3 weeks of age to reduce the risk of
impaired neurodevelopment.
2. Dose
■ Neonates: 10-15 microgram /kg/day.
■ Children: 100 microgram/m 2 /day.
3. Monitoring
■ Clinical assessment
• Physical: Height every 3 months and Bone age every year.
• Mental development and I.Q.
• Sexual: Pubertal development should be within normal.
■ Laboratory assessment: good response is associated with:-
■ T4 on high normal
• TSH on low normal.
□ With neonatal screening, the results of long-term intellectual development have been
satisfactory and intelligence should be in the normal range for the majority of children.

145
 Diabetes
mellitus
Definition
Diabetes mellitus is the most common endocrine and metabolic disease in childhood characterized
by insulin deficiency and or resistance.

Types

1. Type I diabetes: in children

2. Type II diabetes: in obese adolescence r adults: rare
3. Monogenic diabetes results from one or more mutations in a single gene, less common,
variable onset, and may present as neonatal diabetes.

Etiology and pathogenesis of type 1 diabetes

■ Type 1 diabetes is an autoimmune disease triggered by environmental factors such as
infections or toxins in genetically predisposed cases.
■ Antibodies formed against B cells, cause B cell damage and decreasing insulin secretion to such
low level where hyperglycemia and ketosis develop.
• 2 factors are important for the development of autoimmune process

1. Genetic susceptibility
There is an association between type 1 diabetes and susceptibility genes related to
human leukocyte antigen (HLA) in chromosome 6.
6% risk of developing diabetes by 20 years of age for each sibling if a child develops
the disease, rising to 10-20% for a non-identical twin and 30-70% for an identical twin.
The increased risk of a child developing diabetes if a parent has type 1 diabetes
(6-9%) if the father is affected, (2-4%) if the mother is affected).

2. Environmental predisposing factors: the most important are:

• Viruses: Mumps, chicken pox , congenital rubella and hepatitis, Coxsackie virus B4 and
CMV
■ Earlier exposure to cow's milk (type 1 diabetes is less in breast fed babies).
• Chemical toxins e.g. accidental ingestion of rodenticide.

• There is association between type 1 diabetes and other autoimmune disorders e.g. acquired
hypothyroidism

146
Comparison between type I and type II
diabetes
Character Type 1 Type II

Etiology Polygenic (Multifactorial) Polygenic

Incidence Childhood: 90% or more of all Adults, less than 10% of

young diabetic young diabetics
Onset, course, duration .
Onset
Acute and rapid Insidious
. Course
Severe ketosis is common Ketosis is rare
Insulin
. Secretion
Decreased
. Sensitivity Absent or low
Decreased
. Dependence Normal
Uncommon
Permanent, total and
severe
Association
. Autoimmune disorders
. Obesity Present Absent
Absent Severe

147
 Pathophysiology of Diabetes mellitus and diabetic ketoacidosis

Anti
Cortisol, insulin
Glucagon, Epinephrine
Insuli

t
n

1- Carbohydrate 2- Lipid 3- Protein

Glycogenolysis Lipolysiss
Gluconeogenesis Free fatty acids 4* Protein synthesis
ketone bodies k_—
4* Glucose utilization 4* Catabolism
(\
Ketonemia
-
Hyperglycemia *
* Ketoacidosis Weight loss 4*
. Glucosuria ketonuria Growth failure
\-----------------------/
. Polyuria:osmotic
s-----------------------/
, Water +elctroytes loss y

Clinical picture
> It is uncommon before the age of 1 year, but the incidence rises during the early
school years to reach a peak at 12-13 years. There are peaks of presentation in
spring and autumn months

> Diagnosis at an early stage of the illness is important in order to prevent

development of diabetic ketoacidosis, so referral to a specialist team must be done
immediately once the diagnosis is suspected

> Diabetic ketoacidosis requires urgent recognition and treatment as it carries a

significant risk of mortality in children and young people.

1. Polyuria, polydipsia and recent weight loss: the main presentation. The duration of symptoms is
usually less than 1 month in most cases
2. Secondary nocturnal enuresis (Bed wetting by night if previously trained) due to polyuria
3. Diabetic ketoacidosis represents the initial presentation in 10-20% of cases.

Complications
Acute complications
1. Diabetic ketosis (see later)

148
2. Infections: (urinary tract infection- vaginal and pedal candidiasis)
3. Hypoglycemia : due to insulin overdose

Chronic complications
1. Microvasculopathy (retinopathy-sensory and autonomic neuropathy, nephropathy)
2. Associated autoimmune diseases: celiac disease or autoimmune thyroiditis
3. Delayed puberty
4. Ischemic heart disease
5. Diabetic foot: Feet infection with neuropathy and vasculopathy

Laboratory diagnostic criteria

Pre-diabetes
1. Fasting plasma glucose from 100 mg/dL to 125 mg/DI -> impaired fasting glucose OR
2. 2 hours plasma glucose in oral glucose tolerance test from 140 mg/dL to 199 mg/dL ->
impaired glucose tolerance. OR
3. Hb A1C from 5.7 to 6.4 % (HbAlC is: Glycosylated hemoglobin is formed from irreversible non enzymatic
binding of glucose to the N terminal of hemoglobin. It reflects the average plasma glucose over the previous few
months

Diabetes
1. Fasting plasma glucose: >126 mg/dl. (fasting = no caloric intake for at least 8 h)
2. 2 hours plasma glucose during oral tolerance test: >200 mg/dl.
3. Random blood glucose: >200 mg/dl in the presence of diabetes symptoms.
4. Raised glycosylated hemoglobin: > 6.5 %

Differential diagnosis
1. Nocturnal enuresis,
2. Causes of polyuria and polydipsia e.g. diabetes insipidus and chronic renal failure
3. Differential diagnosis of DKA : see DKA

Treatment

Exercis
e

Child with diabetes should be hospitalized in diabetic unit to start treatment plan and
to teach the child and parents the proper management

149
 1. Insulin
therapy

a) Nature
Recombinant DNA, concentration is 100 U/ml (Insulin types: see table below)
Dose adjustment
• There is no fixed dose for insulin, the dose is individualized. The total daily dose ranging
between 0.6-1.5 unit/kg/day
• The dose is adjusted according to repeated blood glucose estimation
b) Mode of administration
• Subcutaneous injection(insulin pen or by syringe with short needle):
■ Continuous subcutaneous insulin infusion delivered by a micro-processor pump, d)
Regimen:
• Basal bolus insulin regimen. Bolus insulin: three boluses with short-acting or rapid acting
insulin analogues before each meal.
■ Basal insulin: intermediate or long-acting insulin (see figure below).
4 Mixed insulin is not preferred in children

Basal-bolus regimen
Three times daily short-acting boluses and
one long-acting basal dose of insulin

Type of insulin
Onset Peak Duration
(length of time before insulin time period when insulin is how long insulin
reaches bloodstream) most effective) works

Ultra-short Lispro, Aspart, Glulisine

10 - 30 minutes 30 min-3 hour 3-5 hour

Short acting Regular 30 minutes -1 hour 2-5 hour Up to 12 hour

Intermediate NPH 1 - 2 hours 4-12 hour 14-24 hour

acting

Long action Argine, Detemir, Degludec

3 - 4 hours Minimal peak Upto 24 hour

Mixed form Combined short acting (or rapid acting analogue)and intermediate acting at
different ratios: 30/70 or 50/50 or others

150
 2.
Diet

a) Frequency
• 3 main meals and 3 snacks between meals and before going bed.
■ Snacks are given also before exercise to avoid hypoglycemia

b) Composition: a healthy diet is recommended with:-

• Carbohydrate (better complex carbohydrate) presents 60 % of caloric requirement. A
carbohydrate counting is important for optimum glucose control.
■ Fat: 25 % of total requirement (low fat): plant fat or oils, are preferred than animal fat
■ Protein: 15 % of total caloric requirement.
• Fibers: diet should be food high in fibers as it provide sustained release of glucose.
• Minerals and vitamins should be encourage

3. Exercise
It should be encouraged as it increases the number of insulin receptors in the muscles
and improves glucose utilization.

4. Self-Blood glucose monitoring

■ Regular blood glucose measurements by glucometer
■ The target blood glucose: Fasting 80-120 mg/dl -Postprandial 100-140mg/dl
• It is very important for early detection and management of hypo and hyperglycemia
■ Every 3 month: Hb Al C should be measured to ensure it is in the good control range
(4.5% - 6%)

Insulin Glucometer
DumD

151
Diabetic
ketoacidosis
Definition
Acute metabolic derangement resulting from failure of insulin-dependent glucose metabolism

Pathophysiology ; see diagram page :

1. The main underlying defect is insulin deficiency, resulting in hyperglycemia
and impaired tissue glucose utilisation, with increased farry acids
metabolism and ketone production.
2. Ketones cannot be metabolized because of deficient insulin and
carbohydrate metabolism.
3. Glucose and ketones are increased in plasma and excreted in urine, resulting in osmoting
diuresis with fluid loss.
4. Ketones lead to metabolic acidosis. Dehydration, acidosis and impaired glucose metabolism
lead to increased release of stress hormones which have anti-insulin effects, exacerbating the
process.

Precipitating factors:
1. Infections
2. Insulin under dosage
3. Trauma: physical or psychological

Clinical picture
□ Suspect in:
1. Known diabetic child who appears sick and/or has any of the precipitating factors but DKA
can be the 1 st presentation of diabetes
2. Preceding symptoms: Weight loss - polyuria - polydipsia

□ Early manifestations
• Vomiting and abdominal pain (excretion of ketone bodies in the stomach)
□ Late manifestations (complications)
■ Dehydration and may be shock: due to vomiting and polyuria.
■ Deep rapid breathing due to metabolic acidosis + acetone odor of breath
■ Drowsiness due to cerebral depression and may be coma
■ Depression and arrhythmias of the heart from acidosis and electrolyte disturbances

investigations

152
1. Blood glucose: hyperglycemia (blood sugar above 200 mg/dl)
2. Blood gas analysis: metabolic acidosis (pH<7.3, bicarbonate <15 mEq/L)
3. Urine analysis: glucosuria and ketonuria
4. Urea, creatinine and electrolytes (especially potassium)
5. Evidence of a precipitating cause e.g. infection (blood picture, blood and urine cultures)

Differential diagnosis
1. Causes of respiratory distress (deep rapid respiration of acidosis)
2. Causes of metabolic acidosis
3. Causes of dehydration (see GIT)
4. Causes of acute abdominal pain and vomiting (see GIT)
5. Causes of coma and disturbed conscious level

Treatment
Hospitalization, better in ICU
1. Initial measures
A: Open the airway. B: Oxygen therapy. C: IV line.

2. Fluid therapy
a) Resuscitation (Shock therapy)
10 mL/Kg normal saline in 30-60 min. for those with severe dehydration or severe
DKA (pH<7.1 or bicarbonate <5mEq/L) (could be repeated but don't exceed 30 ml/kg)
If the patient is shocked give bolus of 10 -20 ml /kg isotonic saline 0.9% rapidly and
reassess (could be repeated but not exceeding 30 ml/kg)
b) Deficit therapy : according to the degree of dehydration
Deficit (litres) = % dehydration x body weight (kg)
c) Maintenance: According to body weight or surface area
• First 10 kg of body weight: 100 ml/kg/24 hours.
• For each kg from 11-20 kg: 50 ml/kg/24 hours
• For each kg above 20 kg : 20 ml/kg/24 hours
1. The total fluid (deficit plus maintenance) are given over (48 hours). Correction must
be gradual, rapid rehydration -> cerebral edema

i Use normal saline (0.45% saline is used in hyperosmolar cases).

When blood glucose has fallen to< 250 mg/dl add glucose 5% to the IV fluids to avoid
hypoglycemia
A shock therapy should be subtracted from the total working fluid
4 If the patient shows mild to moderate dehydration start the deficit + maintenance therapy
without bolus fluids

3. Insulin therapy

153
 • Started after resuscitation, after one hour from fluid therapy
• Continuous low dose IV infusion method. NO BOLUSES
• O.lunit/kg/hour, adjust the dose (rate of infusion) according to the blood glucose level.
Infusion must be continued until correction of ketoacidosis
• Monitor the blood glucose regularly aiming for gradual reduction as rapid reduction -
^cerebral edema.
• When glucose reaches 250mg/dl, glucose is added to fluids to maintain glucose >200 mg/dL
• When metabolic acidosis is corrected and the patient can tolerate feeding, sub cutaneous
insulin is given then intravenous insulin is stopped

4. Acidosis
• The use of bicarbonate for correction of acidosis in DKA is generally not
recommended except in case of severe metabolic acidosis not
responding to therapy (pH 7 or less)
• This is because:
a) Most cases will be self-corrected by fluids and insulin

b) Bicarbonate can exacerbate hyperosmolarity and electrolyte disturbance

c) Alkali therapy may result in alkalosis that has its own hazards.

i Resistant acidosis: suspect sepsis or renal failure

5. Potassium therapy
• Potassium is added 30-40 mEq/L after the resuscitation, after the first hour and after the
patient passes urine provided K is not elevated.
• Initial plasma potassium may be low or high but it will fall following treatment with insulin
and rehydration
• If hypokalemia is present, it should be urgently treated

6. Clinical and laboratory monitoring

• Hourly capillary blood glucose (strips)
■ Plasma glucose, Na, K, blood gases and urinary ketones (plasma ketone by strips if
available) and repeat every 2-4 hours
• Renal functions, CBC and sepsis screen if suspected

7. Management of complications
• Shock: hypovolemic (polyuria, vomiting & dehydration) or septic
■ Brain edema from rapid correction of hyperosmolarity and hypovolemia and from cerebral
ischemic hypoxia (shock)
• Pulmonary edema from hyperosmolarity and HF(2ry to acidosis)
• Cardiac arrhythmias (secondary to acidosis and electrolyte disturbance especially K)

154
 Introduction to renal disorders

Functions of the Kidney

1. Regulation of fluid balance (Water homeostasis)
2. Regulation of electrolyte balance (Na, K, Ca, P0 4 )
3. Regulation of acid-base balance
4. Regulation of blood pressure
5. Excretion of waste products
6. Vitamin D activation
7. Stimulation of erythropoiesis

Anatomy

Renal Artery

Cortex Kidney

Medulla
Ureter

Urinary Bladder

Urethra

Kidney is formed of:

• Cortex (outer zone): Contains glomeruli, proximal & distal tubules and collecting ducts
• Medulla (inner zone): Contains loop of Henle, vasa recta & collecting tubules

Draining system for urine is formed of:

• Collecting ducts, minor calyces, major calyces, renal pelvis
• Ureters, urinary bladder & urethra

Microanatomy
- Nephron is the functional & structural unit of the kidney (1 million nephrons/Kidney)
- It is formed of:
l.Glomerulus: formed of
■ Bowman's capsule: formed of visceral layer (called podocytes) & parietal layer

155
 ■ Tuft of capillaries supplied by afferent arteriole & drained by efferent arteriole
■ Mesangium (formed of mesangial cells & matrix): between glomerular capillaries
2.Tubule: proximal convoluted tubules, loop of Henle and distal convoluted tubules

Filtration barrier is formed ot

1. Endothelial cells of glomerular capillaries: fenestrated

2. Capillary basement membrane (GBM): formed of type IV collagen, proteoglycan...
3. Epithelial cells of the visceral layer of Bowman's capsule (= Podocytes): podocytes have
foot processes which are implanted on the glomerular BM leaving filtration slits (covered by
diaphragms)

Filtration barrier is effective in preventing proteinuria due to:

1. Size-selective properties: fenestrations prevent passage of high MW substances
2. Charge-selective properties: Negative charges in GBM repel proteins

Afferent nitration endotheli

arteriole
memor um
ane

Glomerulus Glomerular capillary

156
 E/M picture of the filtration
barrier
Investigations of Renal Diseases

1. Laboratory
a) Urine
■ Urinalysis
o Physical: Color, reaction (pH= 5-7), specific gravity (1015-1025)
o Chemical: Proteins, Hb, bilirubin, glucose
o Microscopic:
RBC (< 5/ HPF)
Pus cells (< 5/HPF)
Casts: indicate glomerular affection LJP/C ratio
■ Urinary Protein / Creatinine ratio tzzz£> • Normally < 0.2
• Proteinuria = 0.2-2
■ 24-hr urine protein
• Heavy range proteinuria
■ Urine culture & sensitivity >2
b) Blood i........... J
■ Kidney function tests (KFTs): serum creatinine & urea
■ Electrolytes: Na, K, Cl, Mg
■ Ca, PO4 , Alkaline phosphatase
■ Blood gases: Acidosis in renal failure & RTA
■ CBC: Anemia in renal failure, Leukocytosis in pyelonephritis
■ Others: Albumin, cholesterol, complement; C 3 , C 4 ,...

2. Imaging
a. Renal ultrasonography (US)
o Determination of the size, site, renal echogenicity
o Can detect dilated system (hydroureter and hydronephrosis): Obstructive uropathy
o Can detect renal stones, renal cystic diseases, hypoplasia, dysplasia
o Bedside and non-invasive
b. Plain X ray: Urolithiasis (renal stones) and nephrocalcinosis
c. Voiding cystourethrogram (VCUG):

157
 o For diagnosis of vesico-ureteric reflux (VUR) and posterior urethral valve
o Invasive (urinary catheter is required)
o High radiation dose
d. CT, MRI: Renal cysts & renal tumors
e. Renal scan: Detection of renal scarring and estimation of renal function (total and
split)
f. Intravenous pyelography (IVP):

o Rarely used in children

o Risk of contrast-induced nephropathy
3. Renal biopsy: US guided, the obtained tissue should be examined by
o Light microscopy: Structure of the glomeruli and interstitium
o Immuno-florescent: Detect immunoglobulin and complement deposition
o Electron microscopy: Structure of podocytes and GBM

Proteinuria
Definition
- Proteinuria is excretion of abnormal amounts of protein in urine.
- Normal urinary protein excretion is < 4 mg/m 2 / hour or urinary Protein/Creatinine ratio <
0.2
- Heavy-range proteinuria: Urinary Protein/Creatinine ratio > 2 or urinary protein excretion >
40 mg/m 2 /hour
- 24-hr urine protein has largely been replaced by the (spot Protein/Creatinine ratio)

Classification
a. According to the duration:
• Transient: Fever, exercise, seizures. Common on random urinalysis
■ Persistent

b. According to the origin:

• Glomerular: Nephroti\c syndrome, glomerulonephritis...
• Tubular: Acute tubular necrosis, tubular disorders as cystinosis...

Orthostatic (Postural) Proteinuria

• Common cause of persistent proteinuria
• Proteinuria occurs in the upright position and disappears in the supine position
• Etiology: Altered renal hemodynamics (compression on the left renal vein)
• Diagnosis: First morning sample is free
• Proteinuria is < 1 g/day
• No hematuria, edema, hypoalbuminemia, hypertension or renal impairment
• Prognosis: Benign condition
• Treatment: Reassurance

158
Definition
It is a clinico-laboratory syndrome characterized by 4 essential features:
1. Generalized edema
2. Heavy-range proteinuria (Urinary protein / creatinine ratio > 2 or urinary protein
excretion > 40 mg/m2 / hr)
3. Hypoalbuminemia (Serum albumin < 2.5 g/dL)
4. Hypercholesterolemia (Serum cholesterol > 200 mg/dL)

Classification
Nephrotic syndrome (NS) can be classified according to the age of onset into:
A. Congenital NS: First 3 months
B. Infantile NS: 4-12 months
C. Childhood NS: After the 1 st year of life

Etiology
1. Idiopathic (lry) NS (90%); Renal pathology may be one of these pictures:

a. Minimal change NS (MCNS)* [85%]

The 3 types may represent different diseases
b. Mesangial proliferation or a spectrum of a single disease
c. Focal segmental glomerulosclerosis (FSGSf

2. Secondary NS (10%)
a. Collagen-Vascular diseases: SLE & Henoch-Schonlein purpura
b. Infection: Malaria, Schistosomiasis, HBV & HCV
c. Malignancy: Lymphoma
d. Drugs: Penicillamine, Gold

Congenital Nephrotic Syndrome (CNS)

- Special type of NS manifesting at birth or during the first 3 months of life
- Poorer prognosis
- Etiology: Primary (genetic mutation in podocyte proteins; e.g., nephrin, podocin...)

Secondary: Congenital infection (TORCH)

- C/P: Generalized edema, large-sized placenta, hypothyroidism (urinary loss of TBG)
- TTT (Mainly supportive): IV albumin & diuretics, nutritional support, ACE inhibitors
(e.g., captopril), unilateral or bilateral nephrectomy (reduce protein loss) &

Pathophysiology
A) Heavy-range proteinuria ( /f't Glomerular capillary permeability)
- Glomerular structural defects (Podocyte injury or genetic mutation in podocyte proteins; e.g.,
nephrin, podocin...)
- T-cell dysfunction

159
B) Hypoalbuminemia: due to proteinuria

C) Generalized edema
Due to Hypoalbuminemia (4/4' Oncotic (osmotic) pressure —►Edema)
D) Hyperlipidemia due to:
- 4/ 4, Lipoprotein lipase (2ry to urinary loss)
- 't'f Hepatic synthesis of lipoproteins (2ry to hypoalbuminemia)

Minimal Change Nephrotic Syndrome

Incidence
■ It is the commonest cause of NS in children (85% of all cases of NS)
■ Commonest age: 2-6 years
■ Sex: (d':? = 2:1)
■ Most cases (80%) are steroid sensitive

Pathophysiology (See before)

A) Heavy-range proteinuria
B) Hypoalbuminemia
C) Generalized edema
D) Hyperlipidemia

Pathology
* L/M: No change or mild mesangial proliferation

■ E/M: Fusion (effacement) of the foot processes of podocytes

Clinical Picture
1. Generalized edema:
• Site of onset: Periorbital (more apparent in morning and decreases by the end of the
day)
• March: Then becomes generalized (LL, ascites, pleural effusion, scrotal / vulval edema)
• Character: Pitting

2. Respiratory distress may develop due to pneumonia, pleural effusion or marked ascites
3. Abdominal pain may develop due to mesenteric hypoperfusion, gastritis or peritonitis
4. No persistent hypertension, No hematuria
5. NS has a relapsing nature; often triggered by upper respiratory tract infection

160
 Complications
1. Infection (The major complication)
Predisposing Factors:
■ Edema, ascites "culture medium"
■ Urinary loss of Immunoglobulins

■ Decreased production of opsonins that facilitate phagocytosis of capsulated

bacteria-> e.g. pneumococci is the
commonest

■ Steroid and immunosuppressive therapy

Organisms: Pneumococci and Staphylococci are the most common
Site of
infection:
■
Peritonitis
* Sepsis, pneumonia, cellulitis, UTI

2. Thromboembolic events:
Predisposing Factors:
■ Hemoconcentration
■ Hyperlipidemia

■ Urinary loss of natural anticoagulants (Antithrombin III, Protein C & S)

Site:
* Deep venous thrombosis (DVT)
* Pulmonary embolism

3. Hypovolemia: Precipitated by aggressive diuresis or diarrhea

4.0ther complications: Respiratory distress, abdominal pain & dyslipidemia

Investigation
s 161
A) Laboratory
a. Urine
• Urinalysis: Proteinuria (3+ or 4+)
• Urine protein/Creatinine ratio > 2
• 24 hour urine proteins: > 40 mg/m 2 / hr (needs timed urine collection which is difficult)
• Proteinuria is selective (Low MW proteins)

b. Blood
• Serum albumin < 2.5 g/dL
• Serum cholesterol > 200 mg/dL
• KFT: Normal
• Complement (C 3 & C4 ): Normal (No consumption)

B) Imaging: Renal U/S

C) Invasive: Renal biopsy (not routine); indicated in:

a. Pre-treatment (when Minimal chang nephrotic is unlikely):
■ Age at onset < 1 yr or > 10 yrs
■ Gross hematuria
■ Persistent hypertension
■ Renal impairment
■ Hypocomplementemia (>pC 3 and/or C4 )
■ Family history of NS

b. Steroid resistant NS (SRNS) - Failure to achieve remission after 4-6 weeks of steroid
therapy

Differential diagnosis of Nephrotic syndrome

1. Causes of generalized edema

Mechanism Important clinical manifestations

Nutritional Hypoalbuminemia (4'4' OP) Kwashiorkor (Ascites is rare)
Hepatic Hypoalbuminemia (4'4' OP) Jaundice, hepatomegaly...
Cardiac Tachycardia, Tachypnea, Tender
't't Venous pressure
hepatomegaly

Allergic TT Capillary permeability History + Itching + Urticaria

Proteinlosing Hypoalbuminemia (4'4' OP) Diarrhea

enteropathy

2. Other renal diseases:

■ Nephritic syndrome: Hematuria, oliguria, hypertension

162
 Other causes of
proteinuria

3. Minimal change nephrotic syndrome or non-minimal Nephrotic syndrome

MCNS Non-MCNS

Age 2-6 Any age

Gross hematuria Absent Common

Persistent HTN Normal BP Hypertension

Renal function Normal May be impaired
Complement Normal May be consumed
Selectivity
Selective Non-selective
(Proteinuria)

Renal biopsy Not indicated Indicated (e.g., FSGS...)

Response to steroids
Generally good Mostly poor (SRNS)

Important Definitions

Relapse: Recurrence of edema OR heavy range proteinuria

Remission: Clinical AND Laboratory remission

Frequent relapses: > 2 within 6 months or > 4 relapses in 1 year duration

Steroid dependence: 2 Relapses during tapering or within 14 days after cessation of

treatment

Steroid resistance: Failure to achieve remission after 4-6 weeks of steroid therapy

Treatment

1. Place of Treatment
a. Home management: Most cases with mild to moderate edema
b. Hospital management: 1st attack or relapses with marked edema or complications

2. Supportive Management
' Remember
a. Diet: i
i
■ Salt restriction Diuretics should be given
■ Protein intake: Normal intake or mildly increased 1
cautiously, why?
I
■ Lipid restriction i • Hemoconcentration
■ Fluid restriction in cases of severe hyponatremia i • Hypovolemia

b. Edema
■ Mild: Salt
restriction
163
 ■ Moderate: Diuretics; Furosemide (1-2 mg/Kg/day)
■ Severe: Salt-free albumin + Furosemide (1-2 mg/Kg/day)
c. Infection: Antibiotics (3 rd generation cephalosporin)

3. Specific Management
a. Induction of
remission:
Induction: Prednisone (2 mg/Kg/day); using dry not edematous weight Divided
into 3 doses after meals for complete 4 weeks:
> if the child is steroid-responsive (Maintenance):
o Shift to alternate-day therapy (2 mg/Kg/day Single morning dose)
o With gradual tapering over 3-5 months

x If the child is steroid resistant (SRNS):

o Do renal biopsy (the pathology is usually FSGS)
o Shift prednisone to alternate-day therapy with gradual tapering
o Add angiotensin-converting enzyme inhibitors: adjuvant to reduce proteinuria
o Add other immunosuppressive drugs: Cyclosporin or tacrolimus

Drug Main side effects Monitoring

Cyclosporin , , . .■ Kidney
HTN, nephrotoxicity, hirsutism, gum hyperplasia Functions

, .. Kidney
Tacrolimus
DM, Nephrotoxicity, mental change
Functions

b. Treatment of
RelapsesAs the initial therapy, but with shorter induction and longer maintenance

c. Treatment of frequently relapsing and steroid

dependent NS

- Rational: To decrease the risk of steroid side effects (cushingoid appearance,

hypertension, cataracts, growth failure)
- Medications used: Cyclophosphamide, Mycophenolate mofetil

Drug Main side effects Monitoring

Cyclophosphamide Leucopenia, alopecia, hemorrhagic cystitis CBC

CBC
Mycophenolate Abdominal pain, BM suppression
mofetil

4. Treatment of complications
a. Infection: Antibiotics (Penicillin)
b. hromboembolism: Anticoagulants
c. Hypovolemia: Salt-free albumin

164
 Acute Nephritic Syndrome : Glomerulonephritis

Definition
Glomerular disease due to immune mechanism characterized by hematuria and oliguria
with or without edema, hypertension, heart failure and renal impairment

Etiology
1. Primary
a. Mesangial proliferation
b. Focal segmental glomerulosclerosis (FSGS)
c. Membranoproliferative glomerulonephritis (MPGN)
d. IgA nephropathy
2. Secondary
a. Collagen-Vascular diseases: SLE & Henoch-Schonlein purpura
b. Infection Acute post-Streptococcal glomerulonephritis (APSGN)
c. Vasculitis

Acute post streptococcal glomerulonephritis

Incidence
It is one of the most common glomerular causes of gross hematuria in children

Etiology
- It is an autoimmune following infection with "Nephritogenic strains" of group A 0-
hemolytic streptococci (e.g., 4,12, 49)
- Site of infection: throat (Pharyngitis) or skin (Impetigo)
- Latent period: 1-2 weeks after throat and 3-6 weeks after skin infection

Pathogenesis (Mechanism of renal injury)

1. Immune complex deposition
2. Molecular similarity between Streptococcal and glomerular antigens

Efferent arteriole
High
Pressure

Bowmans
capsule

Glomerula
filtrate

Proliferation of the epithelial cells

Immune complex deposition

165
Pathophysiology
Proliferation of endothelial cells (occlusion of capillaries)
• Proliferation of epithelial cells (crescent formation in severe cases)
• Proliferation of mesangium (mesangial cells and matrix)
• Lumpy subepitheliaI deposits of Ig and complement along the glomerular basement membrane
• Decreased GFR

Clinical picture (Peak incidence = 5-12 years)

A) Acute nephritic syndrome

• History of preceding streptococcal infection (Pharyngitis or skin) 1-6 wks ago
• Hematuria: gross painless, brown, smoky, tea-like or cola-like [Glomerular origin]
• Oliguria: due to decreased GFR
• Hypertension (60% of cases)
• Edema: usually mild (may be generalized if HF or renal failure)
B) Heart failure: Secondary to HTN or hypervolemia
Tachycardia, Tachypnea, Tender liver
C) Hypertensive encephalopathy
Blurred vision, severe headache, altered mental status, coma & convulsions,

Complications
1. Hypertension: encephalopathy, intracranial bleeding
2. Heart failure

3. Acute kidney injury: usually transient but may progress to RPGN;

4. Electrolyte disturbance (Hyperkalemia)

Investigations
1. Laboratory
a. Urine (Urinalysis):
Color: Brown, tea or cola-like or smoky
Proteinuria (mild to moderate)
b. Blood
• KFT (Urea & creatinine): may be impaired

166
 • Evidence of recent Streptococcal infection (T ASOT, throat or skin contact)
• C3 (returns to normal within 4-8 weeks)
• Normal C 4

2. Imaging: Renal U/S

3. Invasive: Renal biopsy is rarely indicated

a. Severe renal impairment (Rapidly progressive GN = RPGN)
b. Persistent hematuria or proteinuria > 6-12 months
c. Normal C 3
d. Persistent hypocomplementemia > 3 months

Treatment
1. Place of treatment
a. Home management: Most cases (complete recovery is the rule)
b. Hospital management: Complicated cases (renal failure, HF, encephalopathy)

2. Supportive Management
a. Diet:
■ Salt restriction Intake = insensible + urine
output
■ Fluid balance: How??>=^
Insensible water loss= 400cc/m 2 /
b. Rest: During the oliguric phase day

3. Specific Management
a. Edema:
■ Salt restriction, fluid balance, diuretics (Furosemide 1-2 mg/Kg/day)
b. Hypertension:
■ Salt restriction, fluid balance, diuretics (Furosemide 1-2 mg/Kg/day)
■ Ca channel blockers (Nifedipine 0.5-3 mg/Kg/day)
c. Antibiotics (Penicillin):
■ For eradication of streptococcal infection
■ Course = 10 days

4. Treatment of complications
a. Renal failure: Fluid balance, diuretics, dialysis (in severe cases)
b. Heart failure:
> Preload reduction: Diuretics
> Afterload reduction: ACE inhibitors
> Inotropes: Dopamine (digitalis should be avoided)
c. Hypertensive encephalopathy: Antihypertensive (IV Hydralazine or diazoxide)

Prognosis Complete recovery > 95% (6-8 weeks), recurrence: extremely rare

Differential diagnosis of nephritic syndrome: Causes of hematuria

167
Hematuri
a
Definition
Presence of blood in urine (Normal urine contains up to 5 RBCs / HPF)

Classification
1. According to the amount: Gross (seen by naked eye) or Microscopic hematuria
2. According to the origin: Upper or lower urinary tract diseases
3. According to the associated symptoms: Symptomatic (Pain, edema...) or asymptomatic

Etiology
1. Glomerular
■ Glomeulonephritis: APSGN is the most common cause
■ Non-minimal change nephrotic syndrome (e.g., FSGS)
■ IgA nephropathy
• Collage IV nephropathies:
- Alport syndrome (hereditary nephritis that may be associated with deafness)
- Thin basement membrane disease
- SLE
• Henoch-Schonlein purpura nephritis
• Hemolytic-uremic syndrome (Hemolytic anemia + Uremia + Thrombocytopenia)

2. Non-Glomerular
■ Urinary tract infection (pyelonephritis & cystitis): the commonest cause
■ Urolithiasis (Stones) and hypercalcuria
■ Sickle cell nephropathy
■ Exercise
■ Anatomic abnormalities e.g., cystic kidney disease
■ Trauma, Tumors (Wilms tumor), Bleeding disorders

Approach to a case of Hematuria Red-brown urine (without

RBCS)
1. Hb (Acute hemolytic crisis)
1..Is
Is it hematuria or not?? 2. Myoglobin (Muscle injury)
not?? Other causes of red or brown urine 3. Drugs: Rifampicin
4. Dyes: Berries, beets...
2.1s it
glomerular??
168
 Glomerular Hematuria Non-Glomerular Hematuria

Color Brown, tea or cola-like, Bright red

smoky
Proteinuria Often present No
Dysmorphic RBCs Yes No
RBC casts Yes
No

3. What is the cause??

History + Examination + Investigations (Discuss briefly)

Investigations
1. Initial investigations:
• Urine: analysis, culture, protein, calcium
• Blood: kidney function tests (Urea and creatinine), albumin, electrolytes (Na, K, Ca,
phosphate),
• CBC, clotting screen, Hb electrophoresis
• Ultrasound

2. Further investigations
• ESR, complement levels & anti-DNA antibodies
• Throat swab and antistreptolysin 0 titer (ASOT)
• Hepatitis markers
• Renal biopsy
• Hearing test (if Alport's syndrome is suspected)

169
 Urinary Tract Infections (UTI)

Definition and Classification

It is growth of bacteria in the urinary system (Urine is normally sterile):
• Upper UTI - Pyelonephritis (Renal parenchyma): Fever and systemic manifestations
• Lower UTI - Cystitis (Urinary bladder): No fever
UTI in the pediatric age group is a well-recognized cause of hypertension and
renal impairment

Epidemiology
• It is a common pediatric infection affecting 5% of all children
■ Male: female = 3:1 (1st year). UTI is much more common in uncircumcised boys
1:10 (>1 year)

Etiology
• E.coli (Most common = 80 %)
■ Others: Klebsiella, Proteus, Pseudomonas, Staphylococci, Streptococcus fecalis

Route of infection
■ Ascending: Commoner
• Blood-borne: mostly in the neonatal period

Vesicoureteral
reflux
Posterior urethral valve
Predisposing Factors
■ Obstructive uropathy (stricture, posterior urethral valve, stones...)
• Vesicoureteral reflux (VUR)
■ Infrequent voiding
■ Hurried micturition
■ Constipation
■ Neuropathic bladder
■ Vulvitis
■ Uncircumcised males
■ Poor hygiene

170
Clinical picture
1. Neonates and infants "Non-specific symptoms"
■ Fever (temperature instability) ■ Vomiting and Diarrhea
■ Failure to thrive and feeding ■ Jaundice
difficulties ■ Abdominal pain
■ Screaming during urination

2. Older children:
a. Pyelonephritis: Renal scar occurs in 30-50%
■ Fever, rigors, loin pain & tenderness of PN
Early TIT risk of scarring
■ Nausea, vomiting & diarrhea
■ Chronic PN: hypertension & renal
insufficiency
Frequency - urgency
b. Cystitis:
■ Dysuria (painful micturition)
■ Urgency (intense desire)
Frequency (frequent micturition)
Incontinence (urine leakage)
Secondary enuresis Loin
Suprapubic pain
Fever is absent or low
grade
Investigations
- The correct diagnosis depends on having a proper urine sample
- Methods of urine collection:
■ Midstream urine collection: in toilet-trained children
■ Urine bag: non-invasive, high risk of contamination, good negative test (rule out
UTI)
^Adhesive part applied to the skin
■ Bladder catheterization
■ Suprapubic aspiration: generally not necessary

Urine collection bag

1. Initial investigations
a. Urine analysis:
■ Pyuria (Pus cells > 5/HPF) is suggestive of UTI
■ WBC casts is suggestive of pyelonephritis
■ Not reliable (false positive & false negative results)

False Positive (Pyuria without UTI) False Negative (UTI without pyuria)
Fever Antibiotics therapy
Dehydration TB

Nephritic syndrome (APSGN) Closed infection (Obstructive uropathy)

171
 b. Urine Culture:
■ It is essential for diagnosis & treatment
■ Colony count > 100,000 single pathogen is diagnostic
* Any bacterial growth in a suprapubic aspirate or catheter sample is diagnostic
■ The presence of more than one organism suggests contamination

c. Others (in pyelonephritis)

■ CBC: leukocytosis & neutrophilia
■ ESR, CRP & blood culture
■ Abdominal US

2. Imaging studies in children with febrile

UTI

Goals
- Detection of anatomical abnormalities that predispose to UTI
- Detection of active renal involvement (infection/ scarring)

Available methods (Indications are controversial and changing)

a. Ultrasonography
• Indications:
o First episode of febrile UTI (pyelonephritis)
o Frequently occurring lower UTIs (cystitis)
■ Value:
o Diagnosis of obstructive uropathy (hydroureter and hydronephrosis) o
Detection of renal scarring
b. Renal scan (DMSA)
■ Detection of renal scarring
■ Estimation of renal function (total & split function)
c. Voiding cystourethrogram (VCUG)
• Indications.
o Febrile UTI with abnormal renal US
o Febrile UTI with abnormal renal scan (DMSA)
■ Value:
o Diagnosis of VUR
o Diagnosis of PUV & neurogenic UB

Normal VCUG

172
 Treatment
- Treatment should be started without delay then modified according to the culture result
- Hospital admission may be indicated if there is severe vomiting, infants < 3 months of age
or with poor oral intake

1. Antibiotic Therapy

Cystitis Pyelonephritis

Drugs Trimethoprim-sulfamethoxazole Ceftriaxone Or

Or Cefotaxime Or
Nitrofurantoin Gentamicin + Ampicillin Or
Or Oral 3 rd gen. cephalosporin (e.g.,
Amoxicillin Cefixime)
Route Oral IV for 5 days then oral

Duration 3-5 days 7-14 days

2. Other Lines (for recurrent UTI)

• Adequate fluid intake
• Frequent voiding
• Ensuring complete bladder emptying
• Avoid/treat constipation
• Antibiotic suppressive therapy (Co-trimoxazole: 1/3 therapeutic dose single daily dose)
• Lactobacillus acidophilus (probiotic): Replaces pathogenic bacteria (prevention
of UTI)
• Cranberry juice: prevents bacterial adhesion

173
 Nocturnal Enuresis

Definition
It is repeated involuntary voiding (urination) at socially unacceptable place or time after the
expected age of bladder control (5 years)

Classification
1. According to the timing
■ Nocturnal: Night time; Good prognosis
• Diurnal: Day & Night; Bad prognosis (may be associated with encopresis)

2. According to the onset

■ Primary: No dry period before
■ Secondary: Dry period > 6 months before

3. According to the associated symptoms

■ Monosymptomatic: Only bed wetting
■ Polysymptomatic: Other symptoms; dysuria, frequency, urgency...

Nocturnal enuresis
Definition
It is repeated involuntary voiding during sleep after the expected age of control (=5 years)

Incidence (male: female = 3:1)

• At the age of 5 years: 20%
• At the age of 10 years: 5%
• At the age of 15 years: 1%

Classification
Onset and associated symptoms (See before)

Etiology
Primary enuresis (80% of cases)
1. Maturation delay of bladder control
2. Genetic factors: Family history is positive in 50%
3. sksk ADH production at night (nocturnal polyuria)
4. Sleep disorders
5. Adenoid hypertrophy

Secondary enuresis (20% of cases)

174
 1. Organic cause (UTI and polyuria due to DM, CRF, sickle cell anemia)
2. Psychological factors (child birth...)

Evaluation
Exclude organic causes (UTI, polyuria)
Treatment of organic causes e.g., UTI...

Treatment
1. Simple Measures: (Children > 4 yrs)
a. Explain to the parent and child that the problem is common and beyond conscious
control so punishment should be avoided.
b. Fluid intake in the evening
c. Urination before sleep
d. Waking the child up few hours after sleep to void
e. Rewarding for dry nights

2. Drug therapy (Children > 6 yrs)

a. Anticholinergic ('f'f Bladder capacity): Oxybutynin
b. Desmopressin (synthetic vasopressin analogue): Single night dose
c. Enuresis alarms (conditioning therapy): Auditory or vibratory alarm is attached to a
wetness sensor in the underwear (wake the child up for urination)

175
 Acute kidney Injury

Definition
■ It is rapid (Hours-Weeks) reduction of renal functions to the point where body fluid,
electrolyte and acid-base homeostasis cannot be maintained
■ It is usually associated with oliguria or anuria
■ Oliguria: Urine volume < 400 cc/m2 /day or < 1 cc/Kg/hour
• Anuria: Urine volume < 30 cc/m 2 /day or < 0.2 cc/Kg/hour
■ The term acute kidney injury is preferred to the previous term (Acute renal failure)
■ AKI include 5 stages (RIFLE): Risk, Injury, Failure, Loss and End-stage
■ It is potentially reversible

Etiol
ogy

Prerenal Intrinsic Renal Postrenal

(Renal hypoperfusion) (Obstructive Uropathy)

1. Hypovolemia 1. Acute Tubular Necrosis 1. Congenital obstruction

■ Dehydration ■ Uncorrected prerenal or
• PUV
■ GIT losses (diarrhea) postrenal ARF
* Stricture
■ Hemorrhage ■ Drugs: aminoglycosides

2. Hypotension 2. Acute Glomerulonephritis 2. Acquired obstruction

■ Shock (all types) ■ Stones and Tumors
3. Hypoxemia 3. Functional obstruction
■ Causes of respiratory 3. Vascular "Vesicoureteric
reflux'
failure * Renal vein thrombosis
• Hemolytic uremic syndrome
4. interstitial nephritis by
nephrotoxic drugs

176
 Pathogenesis and clinical
picture
Oliguria or anuria urine output < urine < 1 ml/ kg/ hour

1 Fluid retention Edema and weight gain

Hypertension
Heart failure and may be pulmonary edema

Fluid in the alveoli

2 Retention of acidic wastes Metabolic acidosis -> deep rapid breathing

3 Retention of potassium Hyperkalemia -^cardiac arrhythmias
4 Retention of water more Dilutional Hyponatremia and Hypocalcemia-}
than Na and calcium convulsions
5 Retention of urea and Hyperosmolarity and Brain edema-} uremic
creatinine encephalopathy and coma
Hypotension, tachycardia, and dry mouth may suggest prerenal failure.
Full bladder, a poor urinary stream, may be found in post renal failure

Investigations
1. Kidney function tests: Urea & creatinine
2. Blood gas analysis: metabolic acidosis
3. Electrolytes: Hyperkalemia, hyponatremia, hypocalcemia

Management of AKI

--

A. Conservative management

B.
Dialysis

C. Specific
treatment
177
A. Conservative management

1. Treatment of oliguria or
anuria

Check hydration status

Hypo-or Normal I Overloa

Volume

Fluid *
I _______I
d

Diuretic therapy
Challenge (Furosemide) (2 mg/Kg/
Volume expansion NS dose) or Mannitol
(20 cc/Kg) over 30 min

May be repeated
I
No response (No
P
urine)
ass urine

Furosemide (10 mg/Kg/

dose)
[Intake = insensible+ urine outputs-
losses]
I
No response
(No urine)
Insensible water loss= 400cc/m7day
Dopamine renal dose (2-5 pg/Kg/
min) + Fluid balance

2. Treatment of metabolic acidosis: NaHCO3

3. Treatment of hyperkalemia

a. Stop all sources of potassium

b. Stabilization of the cardiac muscle: Slow IV Calcium gluconate lml/Kg
c. intracellular shift of potassium

> IV Insulin and glucose

> Inhaled or IV 0-adrenergic agents (salbutamol)
> IV Sodium bicarbonate
d. Potassium excretion: Dialysis

4. Treatment of hypertension, convulsions and associated anemia

178
B) Dialysis
Indications of dialysis in acute kidney injury
1. Anuria or oliguria with volume overload
2. Bleeding (platelet dysfunction)
3. Rapidly rising KFTs
4. Intractable metabolic acidosis or Hyperkalemia

Modalities of dialysis in acute kidney injury

1. Peritoneal dialysis
2. Hemodialysis

C) Specific TTT
1. Urological management of obstructive uropathy in post renal injury
2. Correction of dehydration in pre renal injury

Renal Tubular Disorders

Physiological Considerations
■ Water and electrolytes are freely filtered at the glomeruli
■ Tubular reabsorption and/or tubular secretion determine the final urine composition
■ Bulk movement of solute tends to occur in the proximal portions of the nephron
■ Fine adjustments tend to occur distally

A. Renal Tubular Acidosis

Etiology Inherited (cystinosis) or acquired (some antibiotics)

Classification
1. Proximal RTA (type II): Defect in HCO 3 reabsorption in the proximal convoluted
tubules
2. Distal RTA (type I): Defect in H secretion in the distal convoluted tubules
Clinical picture
1. Polyuria, polydipsia, dehydration, failure to thrive
2. Acidotic breathing (rapid and deep)
Investigation Metabolic acidosis, hypokalemia
Treatment Alkali therapy and potassium supplementation

179
B. Bartter syndrome

Etiology Defect in NaK2CI channel in ascending limb of Henle (autosomal recessive)

Clinical picture
1. Polyuria, polydipsia, dehydration, failure to thrive
Investigation Metabolic alkalosis, hypokalemia
Treatment Potassium supplementation

C. Nephrogenic diabetes insipidus

Etiology and Classification Inability to produce concentrated urine due to:

1. Central diabetes insipidus: Defect in ADH secretion (brain tumors and trauma)
2. Nephrogenic diabetes insipidus: Defect in ADH action (mostly mutation in V2 receptors)

Treatment
1. Central diabetes insipidus: Desmopressin (ADH analogue)
2. Nephrogenic diabetes: Hydrochlorothiazide (paradoxical effect)

RENAL TUBULAR TYPE 1 DISTAL ETA

ACIDOSIS
AFFECTS THE BEHAL TUBULES AND IMPAIRED UO(NE RENAL
HYDROGEN ION > 5 HYPOKALEMIA 5TONES
TYPE 2
H 5

RESULTS IN A HYPERCHLOREMIC SECRETION P

NORMAL
METABOLIC SERUM
ACIDOSIS ANION
WITH A PROXIMAL RTA
GAP

BICARBONATE
REABSORPTION

high urine
pH INITIALLY,
LATER < 5.5

HYPOKALEMIA

BOWMANS LOOP COLLECTING

PROXIMAL TUBULE DISTAL TUBULE
capsule OF HENLE DUCT

180
 Chronic kidney disease

Definition
■ It is progressive and usually irreversible reduction of renal functions
■ Symptoms do not usually develop until 60-80% of renal function is lost
• Renal function is calculated by measurement of glomerular filtration rate (GFR)
■ GFR can be roughly estimated by Schwartz formula
■ Normal GFR is > 90 ml/m 2 /minute GFR = 0.5 x Height
(cm)
Serum creatinine

Assessment of GFR (glomerular filtration rate)

■ End-Stage Renal Disease (ESRD): It is the stage of CKD at which survival can not be
maintained without renal replacement therapy (dialysis or transplantation). GFR is usually <
15 ml/m2 /minute

Stage Description GFR

(ml/min/1.73m 2 )
Kidney damage with
1 >90
normal GFR
Mild 4,4, GFR
2
60- 89
3 Moderate 4^4* GFR 30-59

4 Severe 4*4, GFR 15-29

5 Kidney failure < 15 (or on dialysis)

Etiology
1. Congenital anomalies
• Aplasia & hypoplasia
* Obstructive uropathy (Stricture, posterior urethral valve...)

2. Urolithiasis (renal stones)

181
3. Genetic nephrotic syndrome: (e.g. congenital nephrotic syndrome)
4. Cystic kidney diseases: Autosomal recessive & dominant polycystic kidney disease
(ARPKD& ADPKD), nephronophthisis...
5. Focal segmental glomerulo sclerosis
6. Chronic glomerulonephritis: Lupus nephritis...
7. Chronic pyelonephritis (e.g., 2ry to VUR): Reflux nephropathy "Scarred kidneys"
8. Metabolic disorders: Cystinosis (inherited proximal tubular dysfunction) and primary
hyperoxaluria (Calcium oxalate kidney stones and/or nephrocalcinosis)

Diagnosis of CKD
■ The symptoms and signs of CKD are few, vague & non-specific
■ Requires high index of suspicion
■ ARF may be the initial presentation of CKD
■ Assessment of growth & measurement of BP should be done routinely
Clinical picture (= Presentation)
1. Growth failure & short stature
2. Delayed puberty
3. Rickets (Non-nutritional, renal rickets)
4. Anorexia & vomiting
5. Chronic unexplained anemia
6. Chronic unexplained hypertension
7. Polyuria, polydipsia and 2 ry enuresis

Investigations
1. Laboratory
a. Urine analysis
b. Blood

• KFTs (Urea & Creatinine): Impaired in stages 2-5

• Hyperphosphamemia & hypocalcemia
• Blood gases: Metabolic acidosis
• CBC: anemia (normocytic)
2. Imaging
• Renal US: Atrophic kidneys, renal cysts, stones...
• X ray: Long bones (Rickets), Left wrist (Delayed bone age)
3. Invasive: Renal biopsy may show picture of the cause only early in the disease

Management of chronic kidney disease

A) Regular Evaluation
a. Clinical: Nutritional status, growth, pallor, blood pressure, rickets
b. Laboratory: CBC, KFTs, GFR, Electrolytes (Na, K, Ca, P), blood gases

B) Genetic counseling and screening

For patients and families with genetic kidney diseases (genetic nephrotic syndrome,
nephronophthisis, cystinosis, etc)

182
C) Treatment

1. Conservative
Indications: GFR > 15 ml/m2 /minute
Components:
a. Diet:
- Protein restriction (should be balanced against the risk of growth failure)
- Salt restriction in cases with hypertension
- CHO & fats: Free intake to supply sufficient caloric intake
b. Growth failure: Recombinant growth hormone therapy
c. Anemia: Recombinant Erythropoietin + Packed RBCs
d. Acidosis: Alkali therapy (NaHCO 3 )
e. Antibiotics: for infection (Avoid nephrotoxic drugs)
f. Rickets: Active form of vitamin D
g. Hypertension: Salt restriction, diuretics & ACE inhibitors (Captopril)
h. Hyperphosphatemia & hypocalcemia:
- Phosphate binders: CaCO3 (Aluminum hydroxide should be avoided)
- Calcium supplementation
- Active form of vitamin D

2. Renal replacement therapy

Indications: GFR < 15 ml/m2 /minute (ESRD) or with failure of conservative Rx
a. Dialysis
Types:
■ Peritoneal dialysis
■ Hemodialysis

b. Renal
transplantation
Limit
ations: ■ Availability of a matched compatible
donor
■ Risk of graft rejection

Peritoneal Dialysis Hemodialysis

183
 Blood elements
Blood consists of 3 elements, erythrocytes (red cells), leukocytes (white cells) &
thrombocytes (platelets). All are suspended in the plasma

■ Site of blood cell formation

- 1st 2 month (intrauterine): in the yolk sack
- 2-7 month (intrauterine): in the liver
- Bone marrow starts at the 5th month intrauterine and continues after birth

Erythropoiesis
f
Factors affecting 'l
erythropoiesis Physiology of
1- decreased arterial 02 Shape: RBC
biconcave non
___________________________________
concentration -> stimulate the __y nucleated
liver (intrauterine) or the kidney
later to secrete (erythropoietin)
60% water
which stimulate Erythropoiesis

2- endocrine: gonads - thyroid - 28% hemoglobin

adrenals

3- nutrition : aa - Fe - B12 -Folic 7% lipids-3% CHO

acid-vitamin C-vitE-

2- hematopoietic growth factor Electrolytes - enzymes

Hemoglobin (Hb) composition:

Hb molecule is composed of four heme groups (containing ferrous iron) attached to 4
polypeptide chains which define the type of Hb.
Minor adult Hb (Hb A2)
Fetal hemoglobin (Hb
Major adult Hb (Hb A)
F)

Consists
of
a y a B a 6
Fv J
(■

Y6 B a 6«
J

At birth 70% of Hb about 30 % Less than 1%

6-12 m Below 2% Above 95% 3%

184
 Anemi
a
Definition: Decrease of Hemoglobin or hematocrit concentration below the normal value
for age. The normal range varies with age.
Range:
At birth 15-20 g/dl
2-3 month: decrease to 10 g/dl. Rise gradually with age to 15 g/dl at 15 years

Causes (Classification) of Anemia

1. Decreased RBCs production

DYSHEMATOPOIETIC BONE MARROW FAILURE

ANEMIA

□ Iron deficiency anemia A. Pure red cell aplasia

□ Folic acid &Vitamin B12 □ Inherited: Diamond- Blackfan anemia

□ Acquired with (Parvovirus B19 infection)
(megaloblastic anemia).
B. Aplastic anemia (pancytopenia)
□ Chronic inflammation
□ Congenital: e.g. Fanconi anemia
a Myelodysplasia
□ Acquired: idiopathic or secondary to infections
(hepatitis) -Toxins (insecticide) - irradiation
c. Infiltration of bone marrow: Malignant cell e.g.
Leukemia or Metabolic cells as Gaucher cells

2. Increased RBCs destruction (hemolysis)

A.CORPUSCULAR B. EXTRA CORPUSCULAR (EXTRINSIC)

DEFECTS [HEREDITARY] [ACQUIRED]

a. Membrane defect: Immunologic disorders: Non-immunologic

■ Spherocytosis Usually associated with +ve disorders
■ Elliptocytosis Coombs' test
b. Enzyme defect. □ Sepsis
□ Rh & ABO incompatibility
• G6PD deficiency(A) □ Malaria
□ Autoimmune hemolytic anemia:
■ Pyruvate kinase def. □ Wilson disease
1. Idiopathic
c. Hemoglobin defect: □ Artificial valve
2. Infections (e.g. EBV, CMV &
• Quantitative: □ DIC
Mycoplasma pneumonia)
Thalassemia □ Hemolytic uremic
3. Drug-induced (e.g. methyldopa,
■ Qualitative: Sickle cell syndrome
penicillin)
anemia. □ Hypersplenism
4. Collagen vascular diseases (SLE)
(leads to
pancytopenia)

185
3. Blood loss (hemorrhagic anemia)
■ Acute
o Trauma
o accidents
o Varices
o Surgery
o Bleeding disorders (circumcision in hemophilic patients)

■ Chronic:
o Fetomaternal transfusion
o Parasitic infestations (e.g. ankylostoma, bilharziasis)
o Meckel's diverticulum - cow milk allergy

Iron Metabolism

Dietary requirements:
1 mg of iron must be absorbed / day. (Intake of 10 mg of iron /day). Iron is absorbed 2-3 times
more from human milk than from cow's milk

Absorption:
Luminal border of duodenal mucosa: iron is absorbed in the ferrous form.
Inside duodenal mucosa: it is oxidized to the ferric form and becomes attached to an iron free
protein called apoferritin, to form ferritin. When the available apoferritin is fully saturated with
iron, further absorption by the duodenal mucosa stops.

Distribution:
In the plasma: combined with transferrin as ferric iron.
The iron binding capacity = 250-350 mg/100 ml.
Storage: Iron is then delivered to the liver, spleen, muscle and bone marrow

186
 Iron Deficiency Anemia

Incidence: The most common cause of anemia in infancy

Etiology:
1. Diminished stores
- Anemic mother with deficient iron supplementation
-Premature and twins
2. Deficient dietary iron intake
- Prolonged breast feeding (low iron content but 50% absorbed)
- Excessive Cow milk (higher iron content but 10% absorbed
- Iron poor diet
- Protein energy malnutrition
3. Diminished absorption:
-Chronic diarrhea
-Malabsorption
4. Blood loss:
-Chronic hemorrhage
-Ankylostoma
-Schistosomiasis
-Cow milk allergy
5. Increased requirements: In (adolescents especially girls- acute hemorrhage)

Clinical features:
Onset: above 6 months (more common between 9-24 month)

General symptoms of anemia: Pallor (nail bed - palm - lids) - tachycardia - murmurs - heart
failure- Dyspnea- Easy fatigability
1. Atrophic glossitis
2. Poor appetite
3. Poor concentration and behavioral abnormalities
4. Spooning of the nail
5. Pica: (Geophagia) Eating unusual substances as dirt and mud - gravels-
6. Palpable spleen in 15% of cases

Pale lips, conjunctiva and hand creases Hemic murmur

187
Investigations:
Blood picture.*
- Low Hb.
- Microcytic hypochromic anemia
- Color index = Hb% divided by (RBC X2). It will be below 1
- Reticulocytic count is normal. It shows mild increase with therapy.
Blood chemistry:
- Low serum iron < 50mcg % (normal: 90 -150 pg/dl)
- Low serum ferritin < 10 ng (normal: 30 -150 ng)
- Increased iron binding capacity (normal: 250 -350 pg/dl).
Detect the cause
- Adequate clinical history to discover dietary problems.
- Focused and systemic clinical examination to rule out other causes of anemia
- Stool analysis: to detect Ankylostoma - blood in stool - bilhariziasis
- Endoscopy might be indicated: to exclude peptic ulcer or chronic H-Pylori infection

Differential diagnosis from other causes of hypochromic microcytic anemia:

Disease C/P

Iron deficiency anemia History of inadequate iron supply, blood chemistry, Pica

IS-Thalassemia Trait No response to iron and anemia is usually mild

Anemia of Chronic infection Picture of infection.

Sideroblastic anemia Very rare and might Improve with Vit. B6

Lead poisoning Manifestations of lead toxicity.

Prevention:
1. Adequate supply of iron to pregnant female.
2. Making powdered formula well-fortified with iron
3. Prophylactic iron therapy to premature.
4. Proper weaning by supplying iron containing foods
5. Avoid cow milk introduction in the first year of life
6. Provision of appropriate amount of iron rich food for infants and children according
to their age and economic resources
7. Treatment of cause

Treatment:
Iron therapy:
Oral iron therapy:
- Ferrous sulfate or gluconate 3-6 mg/kg elemental iron in 3 divided doses/day in
between meals, with the higher dose used in more severe cases.
- Failure to respond to oral iron = non-compliance or persistent cause

188
 - Iron supplementation should be continued until the Hb is normal and then for a minimum of
a further 3 months to replenish the iron stores.
Parenteral iron preparations:
- Indications: poor compliance or malabsorption.
- Oral therapy is otherwise as fast, as effective, much less expensive and less toxic.
- Parenteral iron sucrose and ferric gluconate complex have a lower risk of serious reactions
than iron dextran, although only the latter is FDA approved for use in children.
Diet: Rich in iron (Meat, liver, green vegetables) and vitamin C.

Treatment of cause: (Schistosomiasis: Praziquantel) (Ankylostoma: Albendazole)

Packed RBCs transfusion should never be necessary for dietary iron deficiency. Even children
with an Hb as low as 6 g/dL to 7 g/dL due to iron deficiency have arrived at this low level over
a prolonged period and can tolerate it.

Successful ion therapy

BY 1 st DAY: REDUCED IRRITABILITY, IMPROVED APPETITE

By 2 nd day; Erythroid hyperplasia in Bone marrow, show erythroid hyperplasia

By 3 rd day: Reticulocytosis peaking at 5-7 days (good therapeutic test)

By 1 st month: elevated hemoglobin 0.1-0.4 gm/dl/day

4-6 weeks: Increased Stores.

Anemia with malnutrition

Etiology: (usually in kwashiorkor)
-Usually multifactorial
-Protein deficiency, folic acid, B12 deficiency, iron deficiency.
-Red cell hypoplasia in the bone marrow.
-Shortening of the red cell life span.
-Associated infections.
C/P & investigations: of anemia & malnutrition

Treatment: replace vitamins, iron and trace element deficiencies according to WHO

recommendations with treatment of infections, parasites and malnutrition.

Ankylostoma anemia
Etiology: Heavy infestation may lose up to 250 ml. of blood daily in the gastro-intestinal tract
leading to iron deficiency anemia & hypoproteinemia.
Clinical picture:
■ Of iron deficiency anemia.,
■ Edema & signs of malnutrition.In severe forms: heart failure may occur.
Treatment:
Treatment of iron deficiency anemia
Albendazole or flubendazole 100 mg orally twice daily for 3 days.

189
 Chronic Hemolytic Anemias

Pathophysiology
In hemolysis: RBC life span shorten (120 day down to few days)
Bone marrow compensate up to 8 folds (more rapid hemolysis will manifest).

Increased RBC Hemolysis

I------- p---------1
----------
Anemia Hemosiderosis Elevated
Bilirubin

Increased Jaundice - dark

erythropoitein Bilirubin
urine on standing stone

—1- Bone marrow hyperplasia (disfigurement-

reticulocytosis)

2- Reticuloendothelial hyperplasia (Hepatosplenomegaly&

'lymphadenopathy)

Clinical picture:
■ Clinical picture of anemia in general (see iron deficiency anemia)
■ Clinical picture of hemolysis
o Jaundice due to increase blood level of unconjugated bilirubin - excess urinary
urobilinogen, Dark urine on standing
o Hepatosplenomegaly (HSM) and skeletal deformities
Causes of HSM:
1. Destruction of abnormal RBCs.
2. Formation of new RBCS (extramedullary hematopoiesis)
3. Deposition of iron overloads (hemosidrosis)
N.B.: splenomegaly will result in hypersplenism with more severe anemia and
pancytopenia
o Macrocephaly (mongoloid features) of face due to compensatory bone marrow
action:

■ Prominent zygoma, forehead, maxilla with [depressed nasal bridge -

prominent upper central incisors - separation of teeth].

190
 o Chronic iron overload (hemosiderosis) due to repeated blood transfusion which if
untreated causes cardiac failure, liver cirrhosis, diabetes, infertility and growth failure.
o Dilated heart & heart failure: effect of anemia (tachycardia & hypoxia) and effect
of hemosiderosis (cardiomyopathy)

Investigations:
To prove anemia: CBC shows Low hemoglobin
To prove hemolysis:
• Blood film: reticulocytosis (raised reticulocyte) & abnormal appearance of the red
cells (e.g. spherocytes, sickled shaped)

• Blood chemistry: elevated serum indirect bilirubin, serum iron, serum ferritin,
decreased iron binding capacity, decreased the haptoglobin.

• Increased urinary urobilinogen

• Positive direct antiglobulin test (only if an immune cause, as this test identifies
antibody-coated red blood cells)

• X ray findings: (poor value) bone marrow expansion (wide diploid space of the skull -
rarefaction of the outer table - increased trabecular patter

191
Complications:
(1) Complication of long term blood transfusion.
- Hemosiderosis (see below)
- 10% of cases show antibodies with difficulty to find compatible blood
- Infection (HBV- HCV- HIV - Malaria)
- Complication of venous access (infection and bleeding)
(2) Anemic Heart failure
(3) Gall bladder stones
(4) Crises: Aplastic, hemolytic, sequestration - (VOC in SCA).
(5) Deposition of iron in tissues (Hemosiderosis)
(Each 500 ml of blood deliver 200 mg of iron)
• Endocrinal disturbances: Delayed puberty- pituitary dysfunction Diabetes mellitus
(bronzed diabetes)
■ Liver cirrhosis and liver failure
■ Pulmonary hemosiderosis.
* Cardiomyopathy
« Arthropathy
■ Neuropathy
(6) Easy fracture of bones
(7) Growth retardation and delayed puberty
(8) Hypersplenism (mainly in thalassemia)
(9) Autosplenectomy in sickle cell anemia

Hemoglobinopathie
s
General considerations
■ These are red blood cell disorders which cause hemolytic anemia because of reduced or
absent production of HbA (a-thalassemias and P-thalassemias) or because of the production
of an abnormal Hb (e.g. sickle cell disease).
■ a-Thalassemias are caused by deletions (occasionally mutations) in the a-globin gene.
■ P-Thalassemia and sickle cell disease are caused by mutations in the 0-globin gene.
■ Clinical manifestations of the hemoglobinopathies affecting the (3-chain are delayed until
after 6 months of age when most of the HbF present at birth has been replaced by HbA.

192
 Thalassemia

Incidence : P thalassemia is the commonest chronic hemolytic anemia in Egypt

Common in the Mediterranean area, while alpha - thalassemia is rare in Egypt
Inheritance: Autosomal recessive disease
Genetic
s:
Defective synthesis of one of the globin chains beta thalassemia
(The gene is absent or non-functioning): Alfa thalassemia
If the defect in a chain production: a thalassemia.
If the defect in P chain production: p thalassemia.

P thalassemia: 2 genes on chromosome 11

2 gene mutation (homozygous): Thalassemia major (Cooley's anemia)

1 gene mutation (heterozygous): Thalassemia minor
Thalassemia intermedia: moderate severity disease with homozygous mutations

Beta thalassemia major (Cooley's anemia)

Pathogenesis
The body switches from HbF to Hb A at the age of 3 -5 months but the gene of P chain is
defective (production of restricted amount of Hb A)
Free a chain become insoluble and precipitate inside RBC (causing hemolysis).

Clinical picture
(Refer to the clinical picture of hemolytic anemia but NOTE THAT):
Onset: by the2nd half of the 1st year
The course is severe anemia which is transfusion dependent
Most liable for early complications and early development of hypersplenism

Investigation
s ■ CBC: low Hb, microcytosis, anisocytosis, target cells, poikilocytosis.

193
 ■ Hemoglobin electrophoresis or High Performance Liquid Chromatography (HPLC): o In the
affected child: Hb F is markedly elevated (10-90%) with reduced Hb A. o Parents:
increased of Hb A2 > 3.5% (normal: 3%)

Anisocytosis: variation in size Target cells: central area of

Poikilocytosis: variation in density (hemoglobin) with
shape surrounding pallor

Differential diagnosis
- Other causes of chronic hemolytic anemia
- other causes of microcytic hypochromic anemia

Prevention: Genetic counseling, carrier detection & prenatal diagnosis

Treatment
" Supportive treatment
Restrict Iron in diet. Folic acid lmg/day. Hepatitis B vaccine. Calcium and vitamin D

■ Lifelong Repeated packed RBCs transfusions:

10 -15 ml /kg every month to keep Hb level >10 gm/dl (hypertransfusion). Value: Good
activity - Better growth - reduce organomegaly & prevent bone deformation

■ Iron chelating agents: (should be started after 10 times blood transfusion) Desferroxamine
(Desferal): 20 - 40 mg/kg by S.C. Pump over 10 hours, 5days/week. Deferiprone: Oral
chelating agent (25mg /kg/dose, three doses per day) Deferasirox: oral chelating agent
(20-40 mg / kg/ day)

■ Splenectomy]
Indications: Huge splenomegaly or hypersplenism (avoid before the age of 4 years).
Splenectomy care:
o Before splenectomy; Vaccination (pneumococci- meningococci- H. influenza) o After
splenectomy: lifelong daily oral penicillin prophylaxis is advised or Long acting penicillin
prophylaxis

■ Bone marrow transplantation:

- it is curative (best below 3 years)

194
 - It is generally reserved for children with an HLA-identical sibling as there is then a 90% to
95% chance of success (i.e. transfusion independence and long-term cure) but a 5%
chance of transplant-related mortality.

• Gene therapy: Introduction of a functioning gene (under trials)

• Induction of fetal hemoglobin synthesis

o hydroxyurea can stimulate Hb F production
■ Treatment of complications:
- Gall bladder stone: cholecystectomy
- Diabetes: insulin therapy
- Short stature: growth hormone

Prenatal diagnosis
For parents who are both heterozygous for P-thalassemia trait, there is a 1 in 4 risk of having an
affected child. Prenatal diagnosis of P-thalassemia (DNA analysis of a chorionic villus sample)
should be offered together with genetic counselling to help parents to make informed decisions
about whether or not to continue the pregnancy.

Thalassemia minor
I

;□ Most cases are asymptomatic.

) □ The condition is suspected when a patient with microcytic hypochromic anemia fails to
respond to iron therapy.
I

[ n Blood picture: microcytic hypochromic anemia- no obvious signs of hemolysis.

! □ Hemoglobin electrophoresis: Increased HbA2 (minor adult Hb).

Sickle cell anemia

Definition: Formation of abnormal globin chain (abnormal S chain)

Incidence: Common in black race
Genetics
Defect in [3 chain gene show mutation that results in replacement of amino acid number 6 in
the chain (glutamic by valine).
■ Heterozygous (Sickle cell trait) where there is inheritance of HbS from one parent
and a normal (B-globin gene from the other parent, patients are carriers and approximately
40% of their hemoglobin is HbS. As carrier, they do not have sickle cell disease and are
asymptomatic. However, they can transmit HbS to their

195
 offspring. Sickle trait can only be identified as a result of blood tests. Carriers
resistant to infection with falciparum malaria
■ Homozygous (Hb SS): Sickle cell anemia

Pathogenesis

A single amino acid substitution in beta chain result in different Hemoglobin (Hb S) which is less
soluble than Hb A. With hypoxia, deoxygenated Hb S polymerize inside RBCs. Distortion of shape
(sickle shaped) result in easy destruction & occlusion of blood vessels

Clinical picture
(Refer to the clinical picture of hemolytic anemia but NOTE THAT):
1. Anemia with variable severity and frequency of painful vasoocclusive crises that
affect many organs of the body.
2. Onset: by the2nd half of the 1st year
3. The course is varying severity

Complications:
1. Increased tendency for infection
2. Different types of vasoocculsive crises including major orangs of the body like acute chest
syndrome and Central nervous system stroke.
3. Autosplenectomy due to recurrent splenic infarctions may develop

Investigations
1. Prove anemia & hemolysis
2. Blood film: Sickling: Characteristic sickle RBCs in blood film under low 02 tensions.
3. Hb electrophoresis: Hb S is present (> 50%) no Hb
A
Parents: HbS 20-40% HbA60-80%

Prophylaxis
Because of functional asplenia, patients are at increased susceptibility to infection specially to
encapsulated organisms. So, they should be
• fully immunized, including pneumococcal, Hib and meningococcus infection.
■ Daily oral penicillin throughout childhood should be given or monthly injection of long
acting penicillin
■ Once-daily oral folic acid because of the increased demand for folic acid

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 caused by the chronic hemolytic anemia
■ Vaso-occlusive crises should be minimized by avoiding exposure to cold, dehydration,
excessive exercise, undue stress, or hypoxia. This requires practical measures such as
dressing children warmly, giving drinks especially before exercise.

Treatment
□ Treatment of acute crises - Painful crises should be treated with:
1. Oral or intravenous analgesia according to need (may require opiates);
2. Good hydration (oral or intravenous as required);
3. Infection should be treated with antibiotics;
4. Oxygen should be given if the oxygen saturation is reduced;
5. Exchange transfusion is indicated for acute chest syndrome, stroke and priapism.
□ Treatment of chronic problems -
1. Hydroxycarbamide, a drug which increases their HbF production and helps protect
against further crises. It requires monitoring for side-effects, especially white blood cell
suppression.

2. Bone marrow transplant, the only cure for sickle cell disease but is usually only
possible if the child has an HLA-identical sibling who can donate their bone marrow - the
cure rate is 90% but there is a 5% risk of fatal transplant-related complications.

Prenatal diagnosis and screening

1. Neonatal screening using the dried blood spots (Guthrie test) collected in the first week of life
for neonatal screening. Early diagnosis of sickle cell disease allows penicillin prophylaxis to be
started in early infancy instead of awaiting clinical presentation, possibly due to a severe
infection.

2. Prenatal diagnosis can be carried out by chorionic villus sampling at the end of the first
trimester if parents wish to choose this option to prevent the birth of an affected child.

Crisis in chronic hemolytic anemia

1. Sequestration crisis
Cause: For unknown cause, large amount of blood become acutely pooled in spleen Clinical
picture: shock, marked enlargement of spleen and liver & acute anemia Treatment: I.V
fluids - Packed RBCs transfusion - Splenectomy for recurrent cases

2. Hyper-hemolytic crisis
Cause: Patient with sickle cell anemia who have in addition G6PD deficiency.

197
 Clinical picture: acute anemia, hemoglobinuria (dark urine)
Investigations: reticulocytosis - enzyme assay later on Treatment: Packed RBCs
transfusion.

3. Aplastic crisis
Cause: infection with parvovirus B19 result in failure of erythroid precursors production
and maturation
Clinical picture: severe anemia that last for 3-4 weeks
Investigations: reticulocytopenia.
Treatment: Packed RBCs transfusion once or twice over 4 weeks

4. Vaso-occlusive crisis
Definition: Painful crisis peculiar to sickle cell anemia.
Cause:
Hypoxia - infections - Dehydration - Acidosis all deoxygenate Hb S
HbS polymerizes within red blood cells result in sickling. Erythrocytes express a number of
adhesion molecules and adhere to the vascular endothelium resulting in obstruction of
blood vessels

Clinical picture:
1. Bony pains: Hand-foot syndrome which may be the 1st presentation of SCA with

severe pain & swelling (ischemia of the metacarpal and metatarsal bones)
2. Recurrent strokes: neurological defect & poor school
performance
3. Acute chest syndrome: acute chest pain &fever due to
pulmonary infarction
4. GIT ischemia: acute abdominal pain.
5. Ischemic nephropathy.
6. Priapism: fibrosis and impotence.
7. Splenic infarctions (autosplenectomy); spleen enlarged early then regress gradually.

Hereditary Spherocytosis
Genetics: Autosomal dominant form of chronic hemolytic anemia, but in 25% there is no
family history and it is caused by new mutations.
Incidence: more common in Europe
Pathogenesis:
■ A defect in the red cell membrane protein, mainly Spectrin, Ankyrin or band 3.
• This results in the red cell losing part of its membrane when it passes through the spleen.

198
 This reduction in its surface-to-volume ratio causes the cells to become spheroidal, making
them less deformable than normal red blood cells and leads to their destruction in the
microvasculature of the spleen.

Clinical features:
1. Onset: May present with neonatal Jaundice and anemia
It may present later in infancy or childhood
2. The clinical manifestations are highly variable that range from asymptomatic patient
to patient with these clinical features:
Jaundice, anemia, splenomegaly, gallstones

Investigations
1. Prove anemia and hemolysis
2. Abnormal osmotc fragility test
3. Abnormal acidified glycerol lysis test

Osmotic fragility test

Treatment
1. Folic acid daily
2. Blood transfusion & chelation may be required less frequent
3. Cholecystectomy if gall bladder stones are present
4. Splenectomy is indicated for poor growth and severe anemia.
• It is usually deferred until after 5years of age because of the risk of post
splenectomy sepsis.
■ Prior to splenectomy, all patients should be vaccinated against Hib, meningitis C
and Streptococcus pneumoniae and lifelong daily oral penicillin prophylaxis is
advised.

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 Acute Hemolytic Anemias

Definition
It is anemia caused by acute (sudden) and rapid destruction of the RBCs intravascular and in
the spleen.
Causes: see before

Glucose-6-phosphate Dehydrogenase deficiency

Incidence
1. The most common cause of acute hemolysis
2. Geography: It has a high prevalence (10-20%) in individuals originating from central
Africa, the Mediterranean, the Middle East, and the Far East. It is the commonest
RBC enzymopathy

Etiology
1. X linked (predominantly causing symptom in males)
2. Heterozygous female :50% of enzymatic activity (appear normal)
3. Female may be affected (if homozygous or with lyonization)

Pathogenesis
G6PD is the rate limiting enzyme in synthesis of NADPH & reduced glutathione. NADPH &
glutathione provide H+ protect hemoglobin against oxidation
G6PD deficiency results in deficiency in NADPH & glutathione.
If Exposure to Oxidants, Hemoglobin become oxidized to met-hemoglobin and precipitate as
Heinz bodies leading to hemolysis (mainly intravascular)

Clinical picture
1. Neonatal jaundice (mild to very severe), usually in the first 3 days of life.
2. Acute hemolysis (pallor, jaundice, dark urine) precipitated by:

• Infection

■ Drugs and chemicals: Analgesics: Aspirin in high dose - dipyrone. Antibiotics:

chloramphenicol - sulphonamides -quinolones Antimalarials: primaquinechloroquine-
quinine. Naphthalene in mothballs

■ Fava beans

200
Complications: Acute heart failure

Investigations:

■ During the attack:

- CBC: Anemia ( normocytic normochromic)
- Reticulocytosis in blood film (hemolysis)
- Chemistry: indirect hyperbilirubinemia -hemoglobinemia - hemoglobinuria
- Blood film shows Heinz bodies

■ Between episodes:
(Almost all patients have a completely normal blood picture with no jaundice)

■ Estimation of enzyme activity after at least 3 weeks of hemolytic attack, because

immediately after hemolysis, bone marrow release reticulocytes with normal enzyme level
giving misleading normal result.

Heinz bodies^--
*

Fragmented
RBCS

0
Treatment:
■ Urgent packed red cell transfusion (10 ml/kg) is lifesaving in very severe hemolysis
■ Prevention of subsequent attacks: A list containing oxidants materials (drugs, chemicals and
food) should be given to parents.

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DP of the causes of acute hemolysis:
Disease Specific clinical picture Specific Investigations

G6PD History of first intake of beans (G6PD Heinz bodies

deficiency) G6PD assay

Autoimmune 1. History of Drug intake -infection 1. Severe reticulocytosis

Hemolytic within 2 wks. May be Associated
2. Indirect hyperbilirubinemia
Anemia arthritis-skin rash
2. Patient present by severe pallor, 3. Positive direct antiglobulin
jaundice and may be splenomegaly. test (Coomb's test)
3. The most alarming signs
are:
■ Failure to find matched blood for
transfusion

■ Very rapid decline in hemoglobin

after transfusion with recurrent
transfusion needs unless the
patient started
immunosuppressive treatment
with steroids.

Hemolytic 1. History of severe gastroenteritis - Thrombocytopenia

uremic 2. Hypertension - Hemolytic anemia with
syndrome (HUS) 3. Acute renal failure fragmented RBCs in the

4. Hemolytic anemia peripheral blood

5. Purpura may develop due to - Elevated renal function

thrombocytopenia

Traveling to endemic area Pattern of Blood film is diagnostic

Infection
(Malaria) fever

Sepsis Toxic patient (septicemia) CBC (Leukocytosis, Shift to Lt),

Purpuric eruption increased CRP, ESR)

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 Bone Marrow Failure Syndrome: Aplastic anemia (aplastic pancytopenia)

Definition: a reduction or absence of all three main lineages in the bone marrow leading to
peripheral blood pancytopenia.

Clinical picture:
■ Anemia
■ Purpura
■ Fever: persistent fever resistant to treatment - persistent oral fungal infection
■ Specific picture of the cause

Investigations:
■ Blood picture: Pancytopenia
■ Bone marrow examination: hypocellular bone marrow

Causes:
(1) Congenital (inherited):
■ Fanconi anemia: most common
• Dyskeratosis congenital: with dysgenesis in skin & nails
(2) Acquired:
■ Idiopathic: the most common (70%)
• Secondary to
oViral Infection (EBV - hepatitis viruses)
oExposure to radiation
oExposure to toxins as benzene oDrugs: Chemotherapy, chloramphenicol, sulphonamides

D.D. of aplastic anemia: Leukemia - ITP

Fanconi anemia
- Autosomal
recessive
- bone marrow failure which usually appear around the age of 5 years
- Congenital anomalies: microcephaly, microphthalmia, short stature, absent
thumb, absent radius, renal malformations, pigmented skin lesions

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 Investigations
■ CBC will show pancytopenia
■ Bone marrow aspirate and biopsy will show hypocellular bone marrow
■ Chromosomal breakage study (spontaneous and induced): increased chromosomal
breaks of peripheral blood lymphocytes. This test can also be used to identify affected
family members or for prenatal diagnosis.
■ Skeletal survey might show absent thumb or radius
■ abdominal U/S might show renal anomalies

Prognosis:
Affected children are at high risk of death from bone marrow failure or transformation
to acute leukemia.

Treatment
• Supportive therapy :( controlling anemia - infection - bleeding)
• Bone marrow transplantation from normal, HLA- matched donor is the only curative
treatment

Acquired aplastic anemia

Onset: at any age (acute onset) after exposure to toxins, infections, drugs or idiopathic
Clinical Presentation: Spontaneous onset of pallor, purpura and recurrent infections
Investigations:
- CBC will show pancytopenia
- Bone marrow aspirate and biopsy will show hypocellular bone marrow
- Chromosomal breakage study (spontaneous and induced) will be normal

Treatment:
Supportive therapy (controlling anemia - infection - bleeding)
• Mild to moderate cases:
- immunosuppressive therapy (Anti-thymocyte globulin (ATG) and/ or cyclosporine)

• Moderate and Severe cases:

- Bone marrow transplantation (BMT) is the treatment of choice from HLA matched sib. If
not available immunosuppressive therapy

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 Acute leukemia

Definition: malignant proliferation of white cell precursors that occupy and inhibit BM
Risk factors
- Genetic predisposition
- Chromosomalabnormalities
- Exposure to chemicals (benzene - pesticide) or radiation
- Viral infection and immunodeficiency
Incidence: The most common form of childhood malignancies.

Acute leukemia 95% Chronic leukemia 5%

• Acute Lymphoblast leukemia (ALL): • No chronic lymphoblastic leukemia in

75% - good prognosis - (2-5 Years) children

• Acute myeloid leukemia: (20%) poor • Philadeliphia chromosome (t 9; 22) +ve

Prognosis - (> 5 years) (Chronic myeloid leukemia): rare

Clinical features of acute leukemia

Systemic ill-health from infiltration of the bone marrow or other organs with leukemic blast cells.
In most children, leukemia presents insidiously over several weeks but in some children the
illness presents and progresses very rapidly.

1. General malaise,
anorexia
2. Bone marrow
■ Anemia lead to pallor, lethargy
infiltration:
■ Neutropenia lead to infection
• Thrombocytopenia lead to bruising, petechiae, nose bleeds

■ Bone pains
3. Reticulo-endothelial infiltration:
CNS
■ Splenomegaly infiltration
■ Hepatomegaly.
■ Lymphadenopathy Lymphadenopath
HSM
Bone y
4. Other organs infiltration: pain Purpura
■ Testicular infiltration
■ CNS infiltration: Headache, vomiting
Arthralg
Investigations: ia

1. CBC: anemia -thrombocytopenia - WBC (increased, decreased or normal)

2. Peripheral blood film may show blast
cells
205
 3. Bone marrow examination: is essential to confirm the diagnosis (blast cells) and to
identify immunological and cytogenetic characteristics which give useful prognostic
information.
4. Lumbar puncture to identify disease of CSF
5. Chest X-ray to identify mediastinal mass characteristic of t-cell disease

Prognosis varies according to some prognostic factor:

1. Patient age
2. Different subtypes (ALL, AML, T-cell subtype)
3. WBC > 50,0001 mm3 carries poor prognosis
4.Speed of Response to initial chemotherapy

Treatment of ALL:
1. Supportive treatment:
■ Blood & platelet transfusion
■ Treating the infection
■ Hydration
2. Chemotherapy:
Combination of chemotherapy
■ Induction of remission: asparagenase -vincristine -prednisone - cytarabine
■ Intrathecal: methotrexate, hydrocortisone- cytarabine
■ Systemic continuation therapy: 2- 3 years- (6 mercaptopurine - methotrexate}
3. Bone marrow transplantation in relapsing cases

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 Bleeding disorders

Hemostasis describes the normal process that keeps the balance between bleeding and
thrombosis. It takes place via a series of tightly regulated interactions involving cellular and
plasma factors.

There are five main components

1. Coagulation factors - are produced (mainly by the liver) in an inactive form and are
activated when coagulation is initiated (usually by tissue factor (TF), which is released by
vessel injury.
2. Coagulation inhibitors-these either circulate in plasma or are bound to
endothelium and are necessary to prevent widespread coagulation throughout the body
once coagulation has been initiated i.g. protein C, Protein S and antithrombin
3. Fibrinolysis - this process limits fibrin deposition at the site of injury due to activity
of the key enzyme plasmin.
4. Platelets - are vital for hemostasis as they aggregate at sites of vessel injury to form
the primary hemostatic plug, which is then stabilized by fibrin.
5. Blood vessels - both initiate and limit coagulation. Intact vascular endothelium
secretes prostaglandin 12 and nitric oxide (which promote vasodilatation and inhibit platelet
aggregation). Damaged endothelium releases TF and procoagulants (e.g. collagen and
von Willebrand factor, vWF)

Defective hemostasis leads to:

Bleeding: due to defects in the coagulation factors, in platelet number or function.
Thrombosis due to defects in the naturally occurring inhibitors of coagulation (e.g.
antithrombin) or in the vessel wall (e.g. damage from vascular catheters)

Causes of
bleeding: Inherited disorders Acquired disorders

- Haemophilia A (factor VIII deficiency) - Vitamin K deficiency

- Hemophilia B (factor IX deficiency) - Liver disease
- von-Willebrand disease (vWD) - Immune thrombocytopenia
- DIC

Work-up of a case of
bleeding:
□ History taking:
■ age of onset.
■ Family history. 207
 ■ Bleeding history
oSite.
oSeverity: stopped spontaneous, need hospitalization & intervention o Pattern of
bleeding (skin &mucous membrane or deep bleeding in the joint/ muscle)
o Preceding factor as trauma, surgery, infection
■ Drug history
■ Systemic disorder

□ Examination:
■ Vital sign, Assess growth, skeletal examination, organomegaly

□ The most useful initial screening tests are

■ Full blood count and blood film.
• Bleeding time (done if platelet count > 50 X 10 3 / mm 3 ) - screen for platelet function defect
and vascular defects
■ Prothrombin time (PT) - measures the activity of factors II, V, VII and X.
■ Activated partial thromboplastin time (APTT) measures the activity of factors II,
V, VIII, IX, X, XI and XII.
■ Thrombin time - tests for deficiency or dysfunction of fibrinogen.
■ D-dimers - to test for fibrin degradation products (the test is used to diagnose tendency
for thrombosis as it increases in cases of hypercoagulation).
■ Biochemical screen, including renal and liver function tests.

□ Specific tests that confirm the abnormalities detected in the initial tests:
■ Platelet function tests—if bleeding time is prolonged
■ Quantitative Specific coagulation factor assay - select the factor according which is
prolonged PT or APTT or Both or TT

Platelets
Megakaryocytes of the bone marrow, release platelet by budding (fragmentation of the
cytoplasm of mature megakaryocytes
Platelets are non-nucleated cell fragments (short half-life of 7-10 days).
Function of platelets
Adhere and aggregate to seal points of bleeding
Initiation of coagulation
Platelet plays a role in initiation of coagulation and in clot retraction.
Platelet count
Normal platelet count: 150-450 X 10 3 /mm3
Mild Thrompocytopenia: 50 -150 X 103 / mm 3
Moderate Thrompocytopenia: 20 -50 X 103 /mm3
Severe Thrompocytopenia: risk of spontaneous bleeding < 20 X 103 mm3

208
 Purpura
Definition: Minute bleeding due to platelet or vascular defect characterized by purple
petechie and ecchymosis
Causes

Thrombocytopenic Purpura

TT Destruction 4,4, Production

□ Immune: □ Inherited:
- ITP (the commonest) -Thrombocytopenia with absent radii
- Neonatal alloimmune thrombocytopenia (TAR syndrome)
- Systemic lupus erythematosus - Fanconi anemia
□ Non-immune: -Thrombopoeitin deficiency
- DIC □ Acquired:
- HUS - As a part of acquired aplastic A.
- Thrombotic thrombocytopenic purpura - B.M. infiltration (e.g. leukemia)
- Hypersplenism - Drugs (aplasia of megakaryocytes)
- Nutritional (lB12 & folic a.)

Non-thrombocytopenic purpura

Small B.Vs. defects Defective platelet function

- Infections as (Qualitative)
meningococcemia □ Inherited:
- Vitamin C deficiency (scurvy) - Giant platelet syndrome
- Inherited: Ehlar Danlos
□ Acquired:
syndrome -
Marfan syndrome - Uremia
- Immune vasculitis (Henoch- - NSAIDs
Schonlein puprpura)

Immune Thrombocytopenic Purpura (ITP)

Definition:
Acquired generalized hemorrhagic state due to destruction of circulating platelets due to
autoantibodies

Incidence: the most common cause of purpura

• Acute: 85 -90 %: Usually proceeded by nonspecific viral illness or rubella

It is characterized with autoantibodies

• Chronic: 10-15 %: Persistence of clinical and laboratory findings > 12 months. It is related to
autoimmune disease. Hereditary factors may be present.

Clinical features:

209
 ■ Onset: 1-2 weeks after viral illness (age 2-10 years)
■ SC bleeding in the skin:
- Non-blanching not raised purple in color then change within days to green then brown
then fade) [differentiate from insect bites],
- Variable size: petechiae (spots <3 mm), purpura (3-10mm) or ecchymosis (>1 cm)
- Generalized over limbs and trunk and face
■ Bleeding from the mucous membranes: bleeding gums, epistaxis or hematuria
■ Intracranial hemorrhage is the most serious. (1%)
■ Anemia with severe bleeding
■ No other features as hepatosplenomegaly or congenital anomalies

Petechiae Purpura Ecchymoses

Less than 3 mm to 1 More than 1
3mm cm cm

ITP is a diagnosis of exclusion

Careful attention must be paid to the history and clinical features

Investigations:
• CBC:
- Thrombocytopenia, usually < 20,000 / mm3 (Normal: 150,000 - 400.000mm3 )
- May be low Hb due to blood loss.
- Normal WBCs count with relative lymphocytosis.

• Bone marrow
examination:
- Megakaryocytes are normal or increased in number with defective budding

Anti-platelet antibodies: are found in 60 % of

cases.

210
Differential diagnosis:
■ Aplastic anemia: pancytopenia and decreased all precursors of bone marrow
■ Acute leukemia: infiltration of bone marrow by blast cells
■ Other causes of thrombocytopenia.

Treatment:
1. In mild cases:
- Cutaneous hemorrhage only: conservative management and close follow up with direct
platelet count to ensure that the count is safely above 10,000.
- Avoid trauma and salicylate.
- Avoid non-steroidal anti-inflammatory medications
- Advice the parents to attend to clinical care immediately if the child has active bleeding
other than cutaneous hemorrhage like gum bleeding or epistaxis

2. In moderate cases: Persistent muco-cutaneous hemorrhage

- Prednisone: Dose 2 mg/kg/d.
. Action: It inhibits antibody synthesis & phagocytic activity.
. Duration 2 weeks followed by gradual withdrawal
- Intravenous immunoglobulin (IVIG): dose 0.8-1 gm/kg/day, Duration for 2 days.
. Action It causes rapid rise of platelet count (block the phagocytic activity)

3. In severe cases: (severe muco-cutaneous hemorrhage or intra-cranial hemorrhage)

- I.V. methyl prednisolone 20 mg /kg / day for 5 days
- Platelet transfusion after starting steroid +/- Fresh whole blood if needed.
- IVIG.
- Plasmapheresis: (transient effect) (only when others fail).
- Emergency splenectomy: final solution.

4. In chronic cases: (>12 months):

- Careful evaluation for associated disorders
(E.g. SLE: frequent screening of autoantibodies).
- Prednisone & IVIG.
- OR Splenectomy (75% curative).
- OR Immunosuppressive therapy (e.g. Rituximab- azathioprine- Cyclosporine).

Prognosis
Acute serious hemorrhage occurs in the acute phase (1st 2 weeks). In about 80% of children,
the disease is acute, benign, and self-limiting, usually remitting spontaneously within 6 weeks
to 8 weeks.

211
Understanding the Coagulation Scheme
Blood Clot

Red blood cell

Broken blood

Activate
d ciot

The endpoint of the coagulation cascade is generation of fibrin. The three main pathways for
thrombin generation were identified as the intrinsic, extrinsic and common pathways.

Phase I (Intrinsic pathway)

Successive activation of coagulation factors in the presence of phospholipids.
Assessed by activated partial thromboplastin time (APTT) (normal = 25-40 seconds)
It measures clotting factors (XII, XI, IX and VIII)

Phase II (Extrinsic pathway)

This phase can be assessed by prothrombin time (PT) (normal value 11-14 sec)
It evaluates factors VII
Phase III (Common pathway)

Both pathways meet for the splitting of fibrinogen (factor I) in the presence of
thrombin.
common pathway involves factors I, II, V, and X.
Assessed by both APTT and PT. The thrombin time (normal = 15-20 seconds)
assesses the fibrinogen level

212
 Hemophilia

Hemophilia A (Classic hemophilia)

Genetics: X linked disease with reduced factor VIII cone, (more in male)
Incidence: 1/5000 male - 80% of cases of hemophilia.

Clinical features:
1. Bleeding in the neonatal period [circumcision bleeding- prolonged bleeding from heel
prick or venipuncture from umbilical stump]
2. Extensive bruising, hematoma and bleeding with minor trauma
3. Hemarthrosis
. The hallmark of hemophilia
. With trauma or spontaneous
. If repeated: degenerative joint changes and fibrosis (fixed ANKYLOSIS)
4. Spontaneous Bleeding from orifices: epistaxis or hematuria in severe cases
5. Internal organs: intracranial hemorrhage. Intramuscular hemorrhage (e.g. psoas
hemorrhage)

1. Intracranial Hemorrhage
2. Psoas hemorrhage may be fatal
3. Ankylosis
4. Complications of treatment
- Blood born infection (HBV- HCV- HIV -CMV)
- Development of antibodies against transfused factor 8 (5-20%) called inhibitors: . This
result in resistance to treatment
. The condition requires higher dose of factor VIII or bypassing agent (a f VII).
5. Complication of vascular access [difficult cannulation -thrombosis or infection]

Investigations:
1. Phase I coagulation defect (prolonged PTT)
2. Specific factor VIII assay (reduced below normal) Normal > 60% & Carrier 30
-60% (female).
213
 - mild hemophilia 5-30%: (bleeding with trauma or surgery)
- moderate hemophilia 1-5%: (bleeding with minor trauma)
- severe hemophilia < 1%: (spontaneous joint bleeding)

Prevention:
Avoid trauma-aspirin - non-steroidal anti-inflammatory- make sure the child is
vaccinated against Hepatitis B virus - Physiotherapy prevent joint contracture.

Treatment:
1. Cold compress minimize bleeding in mild cases

2. Replacement (essential in moderate or severe cases)

■ I.V. infusion of cryoprecipitate (Plasma concentrate of factor VIII) (Dose: 25 - 50
Unit/ kg every 12 hours). This dose applies to hemarthrosis. Various dose
protocols are present for different types of bleeding.
■ I.V. infusion of Purified plasma derived factor VIII concentrate
■ IV infusion of Recombinant factor 8.
■ Prophylactic F VIII in severe hemophilia (2 times per week)
3. Desmopressin: In mild hemophilia A it increases endogenous release of FVIII
(ineffective in hemophilia B).

4. Physiotherapy specially after immobilization to prevent muscle wasting and joint

contracture

Hemophilia B (Christmas disease) factor IX

Genetics: X linked recessive -15% of alldeficiency
hemophilia due to factor IX deficiency

Incidence: 1 in 30 000 male births

Clinical features: like Hemophilia A but with (delayed onset) - Milder bleeding
Treatment: Fresh frozen plasma or factor IX concentrate (once or every 24 hours).

Von Willebrand disease (Vascular hemophilia)

Genetics Autosomal dominant defect in the production of VW protein
Pathogenesis:
Von-Willebrand Protein play 2 roles
- Facilitate platelet adhesion and
- Protect factor VIII from breakdown (act as carrier protein)
If reduced, it reduces factor VIII activity & defective platelet adhesion.

Clinical features (of Von-Willebrand disease type 1):

214
1. Mild Bleeding tendency; mainly epistaxis, bleeding gums bruising, menorrhagia and bleeding
with surgery
2. Spontaneous hemorrhage is extremely rare

Investigations:
1. Normal platelet counts but defective platelet adhesion (prolonged bleeding time).
2. Prolonged PTT.
3. Reduced level of vW protein & factor 8.

Treatment:
1. I.V. infusion of cryoprecipitate, plasma derived FVIII or vW factor.
2. Desmopressin can help in mild cases
3. Avoid IM injection, aspirin, nonsteroidal anti-inflammatory drugs

Differential diagnosis of hemophilia in general:

• Acquired coagulation defects as liver failure
• Disseminated intravascular coagulation (DIC).

Thrombosis in children

Thrombosis is uncommon in children and about 95% of venous thromboembolic events are
secondary to underlying disorders associated with hypercoagulable states.

Causes:
Inherited thrombotic disorders Acquired thrombotic disorders
- Protein C deficiency DIC
- Protein S deficiency - Hypernatremia
- Factor V Leiden deficiency - Polycythemia
- Anti-thrombin deficiency SLE

Clinically
1. Precipitating factor: like surgery, prolonged bed ridden disease, severe dehydration or
central venous access.

2. Rarely, thrombosis can also be spontaneous without any precipitating illness (e.g.
homozygous protein C disease where the infant present with widespread gangrene in the
first few days of life, what is called purpura fulminans).

3. Adequate clinical suspicion and immediate request for laboratory and radiographic
diagnostic techniques is essential for correct diagnosis and prompt management.

215
 Disseminated intravascular coagulation
- DIC is an acquired syndrome characterized by hemorrhage and thrombotic complications.
(DICI
- It results from activation of the coagulation system by a variety of underlying disorders, (e.g.
infections, trauma, malignancy, etc...).

Clinical manifestations: (variable)

1. In mild cases, bleeding may only be noted at venipuncture sites
2. In more severe cases there may be extensive hemorrhage and thrombosis with end-organ
damage to the kidney, liver, lung, extremities, and central nervous system.

Investigations:
1. Prolonged prothrombin time
2. Prolonged partial thromboplastin time
3. Decrease fibrinogen level

4. Increase FDPs
5. Thrombocytopenia.

Differential Diagnosis:
1. Thrombophillia
2. Hemolytic uremic syndrome
3. Thrombotic thrombocytopenic purpura

Management.
1. Treatment of the underlying primary disease.
2. In patients with clinically significant bleeding replacement therapy with platelets and/or
coagulation factors (fresh frozen plasma or cryoprecipitate) might be needed according to the
clinical condition of the patient.

216
 Blood component therapy
Blood and blood product transfusion can be a lifesaving procedure, but it has risks, including
infectious and noninfectious complications. Acute complications occur within minutes to 24 hours
of the transfusion and the delayed complications may develop days, months or even years after
the transfusion.

Blood products that can be infused:

■ Red blood cells
■ Platelet
■ Plasma products:
o Fresh frozen plasma
o cryoprecipitate
o Immunoglobulin
o Coagulation Factor concentrates
o Albumin

Complications of long-term blood transfusion in children:

1. Iron deposition
■ Heart-cardiomyopathy
■ Liver-cirrhosis
■ Pancreas-diabetes
■ Pituitary gland - impaired growth and sexual maturation
■ Skin - hyperpigmentation
2. Antibody formation (10% of children)
■ Finding compatible blood very difficult
3. Infection
■ Hepatitis A, B, C
- HIV
■ Malaria
■ Prions (e.g. new variant Creutzfeldt-Jakob disease)
4. Venous access (common problem)
■ Often traumatic in young children
■ Central venous access device e.g. Portacath, may be required

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 Rheumatic Diseases of childhood

Arthritis
Definition
Swelling or effusion with redness, limitation of range of motion, tenderness or pain on
motion, increased heat.
It can be acute (< 6 weeks) or chronic (> 6 weeks)

Differential diagnosis of arthritis in children:

1. Infections: Bacterial (septic arthritis),TB and viral (rubella and mumps).
2. Post-infectious: Rheumatic fever.
3. Reactive arthritis
4. Rheumatic and inflammatory diseases: JIA, SLE, Dermatomyositis, Vasculitis,
Sarcoidosis.
5. Seronegative spondyloarthropathy: Juvenile ankylosing spondylitis, IBD, psoriatic
arthritis.
6. Auto-inflammatory disease: Periodic fevers (FMF).
7. Hematological: Sickle cell anemia - Hemophilia
8. Malignancy: Leukemia - Lymphoma - Neuroblastoma
9. Congenital disorders: Marfan syndrome and Ehler-Danlos.
10. Bone disorders: Trauma and benign bone tumors.

Reactive arthritis
Definition
Joint inflammation caused by a sterile inflammatory reaction following a recent infection e.g. .
enteric infection with Salmonella, shigella flexneri, Yersinia enterocolitis, Campylobacter jejune
or genitourinary tract, infection with Chlamydia trachomatis

Duration: It is usually transient (less than 6 weeks).

Pattern of arthritis: oligoarticular, more in LL.
Treatment: supportive for pain.

Toxic synovitis of the hip I

Definition
It is a form of post-infectious arthritis, affecting the hip, more in boys 3-10 years old.

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Clinical picture: Acute onset of severe pain in the hip, with referred pain to the thigh or
knee, for nearly 1 week.
Treatment
Laboratory: ESR and CBC are usually normal.
Hip ultrasound may show widening of the joint space secondary to an effusion
Differential diagnosis: Septic arthritis.

Juvenile idiopathic arthritis: JIA

Incidence: JIA is one of the most common chronic illnesses of childhood.

Etiology: not completely understood (immunogenetic susceptibility is highly considered).

Criteria for diagnosis of JIA (It is a clinical diagnosis, without any diagnostic
laboratory tests):

1. Age at onset: <16 yr

2. Arthritis in >1 joint (definition as before, but NOT RED joints)
3. Duration of disease: >6 weeks.
4. Exclusion of other forms of juvenile arthritis e.g. malignancy.

Types of
JIA
1. Systemic-JIA (SJIA)
2. Oligoarticular JIA
3. Polyarticular JIA :Rheumatoid factor + ve and rheumatoid
factor -ve
4. Enthesitis-related arthritis (ERA)
5. Other types of JIA: psoriatic arthritis, arthritis with inflammatory
bowel diseases and undifferentiated arthritis.
Systemic-JIA (SJIA)

Arthritis in >1 joint with, or preceded by, fever of at least 2 weeks in duration
(daily and spiky) and accompanied by >1 of the following:
■ Non-fixed erythematous rash (related to fever).
■ Generalized lymph node enlargement.
■ Hepatomegaly/splenomegaly or both.
■ Serositis (pleural of pericardial effusion).

Laboratory findings
■ Anemia, leukocytosis, thrombocytosis
■ Elevated acute phase reactants (ESR,CRP and serum ferritin).

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Differential diagnosis: Other causes of fever and arthritis should be excluded
specially malignancy.

Small joints of hands of a 2-year-old boy Rash in SJIA (salmon-coloured, non pruritic,
with SJIA. They are swollen, warm, and macular) (Age at disease onset is usually 1-5
painful. years, arthritis is usuallv Dolvarticular.)

Complications:
Macrophage activation syndrome (MAS) can occur with severe, untreated cases
(pancytopenia and drop in ESR).

Oligoarticular JIA

Arthritis affecting 1-4 joints during the 1st 6 months of disease onset.
■ Incidence: This type accounts for 50% of JIA cases.
■ Peak age at disease onset 2-4 yrs. Girls are more affected than boys (3:1).
■ Pattern of arthritis: Asymmetrical involvement of large joints (knee and ankle).
■ Lab. findings: Positive ANA in 30% of cases.

Prognosis
High risk to develop chronic asymptomatic iridocyclitis (especially in ANA-positive patients),
so screening on regular basis by an expert ophthalmologist is highly
needed in these cases.

A 4-year old child with oligoarticular JIA and posterior

synchiae as a complication of chronic anterior uveitis.

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 Polyarticular
JIA

Arthritis affecting >5 joints during the 1st 6 months of disease onset.
Pattern of arthritis: affection of small and large joints, usually symmetric and can
include cervical spine and temporomandibular joints.
Gender: Girls are more commonly affected.
Peak age at disease onset: 2-4 and 10-14 years old.

Two subtypes:
1- Rheumatoid-factor (RF) positive type: arthritis is more aggressive with higher
possibility to cause deformities and progress to adulthood.
2- Rheumatoid-factor (RF) negative type: more benign arthritic course, but more
prone to uveitis.

A child with RF positive JIA having deformities

(ulnar deviation at the wrist, swan-neck deformity in digits 2,3,4 and Boutonniere deformity at
digit 5).

Enthesitis-related arthritis (ERA)

Arthritis and enthesitis (tenderness at the insertion of a tendon, ligament, joint

capsule, or fascia to bone) with at least 2 of the following:
■ Presence of or a history of sacroiliac joint tenderness or inflammatory lumbosacral pain
(pain during the morning that improves with movement).
■ Presence of HLA-B27 antigen.
■ Onset of arthritis in a male >6 years old.
■ Acute (symptomatic) anterior uveitis.
• History of ankylosing spondylitis, ERA or acute anterior uveitis in a lst-degree relative.

Pattern of arthritis: mainly peripheral joints of the lower limbs are affected, but the axial
skeleton can be involved as well and the condition progresses to juvenile ankylosing
spondylitis.

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5- Other types of JIA: psoriatic arthritis, arthritis with inflammatory bowel diseases and
undifferentiated arthritis.

Treatment
Aim: achieve disease remission, prevent joint damage, and allow normal growth and
development.

1. Drugs:
a. Non-steroidal anti-inflammatory drug (NSAIDs) e.g. Ibuprofen - diclofenac
(oligoarticular)

b. Disease-modifying anti-rheumatic drugs (DMARDs): Methotrexate (1 st line drug

in polyarticular type) - Leflunomide.

c. Biological agents: Anti-tumor necrosis factor-a (Etanercept) 2 nd line in polyarticular

type, Anti-interleu kin-1 (Anakinra) and anti-interleukin-6 (Tocilizumab) in systemic
type following steroid therapy.

d. Steroids: intra-articular steroids (oligoarticular type), systemic steroids (systemic type),

topical steroids (uveitis).

SIDE EFFECTS: Cushing syndrome, growth failure and osteopenia (steroid

therapy should be used with the least dose and duration possible in
children).

2. Physiotherapy: to strengthen muscles and increase the range of joint motion.

3. Periodic slit-lamp ophthalmologic examinations: to monitor for asymptomatic

uveitis

4. Family and psychological support.

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Systemic Lupus Erythematosus
Definition:
It is an autoimmune disease characterized by multisystem inflammation and the presence of
circulating autoantibodies directed against self-antigens. It can affect any organ. Disease
course is characterized by periods of activity and remissions.

Gender: females are more affected.

Age: can occur at any age, childhood-type is more severe with more renal and CNS
affection.

Malar rash.

Oral ulcers.
Discoid rash. Photosensitivitv.

Clinical presentations:
The most common presenting complaints of children with SLE include fever, fatigue,
hematologic abnormalities, arthralgia, and arthritis.
Diagnosis:
American College of Rheumatology (ACR) 1997 Revised Classification Criteria for
SLE requires having 4 of 11 criteria:
1. Malar rash.
2. Discoid rash.
3. Photosensitivity.
4. Oral or nasal ulcers.
5. Neurological: Seizure or psychosis.
6. Nephritis: Consistent renal biopsy, persistent proteinuria or renal casts.
7. Arthritis: Non erosive, > 2.
8. Serositis: Pleuritis, pericarditis or effusion

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 9. Hematological: Hemolytic anemia, leukopenia (<4,000 Ieukocytes/mm3), lymphopenia
(<l,500/mm3), thrombocytopenia (<100,000/mm3).
10. Positive antinuclear antibodies (ANA).
11.Immunological abnormalities: Antibodies to double-strand DNA, anti-Smith Abs,
positive lupus anticoagulant test result, or elevated anticardiolipin immunoglobulin (Ig) G
or IgM antibody.

An updated criteria in 2012 validated 3 more criteria: consumed C3, C4 or CH50, non-
scarring alopecia and positive direct Coombs test in absence of hemolytic anemia. At
least one clinical criterion and one immunological (laboratory) criteria are needed to suspect SLE.

Treatment
1. Sunscreen and avoidance of prolonged direct sun exposure may help control
disease.
2. Hydroxychloroquine: help to control skin and joint manifestation and improve
oucome in all SLE patients.
3. Non-steroidal anti-inflammatory drugs: for mild arthralgia and arthritis.
4. Corticosteroids (oral and IV): the main stay of treatment in SLE.
5. Steroid-sparing immunosuppressive agents: Methotrexate and azathioprine (joint and
blood affection), Mycofenolate mofetil and cyclophosphamine (renal and neurological
affection).

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Juvenile dermatomyositis (JDM)
It is the most common inflammatory myositis in children.

Etiology: multifactorial (genetic susceptibility and environmental trigger)

Clinical picture:
1. Classic rash: heliotropic rash of the eyelids and gottrons papules.
2. Proximal symmetric muscle weakness: with muscle pain and tenderness.
3. Arthritis and arthralgia.
4. Calcinosis: in severe cases

Gottrons papules at the proximal and distal

... Heliotropic rash of the eyelids
interphalangeal joints

Differential diagnosis:
Other causes of myopathy should be considered, including infection-related myositis
(influenza and coxsackivirus), muscular dystrophies (Duchenne),and Guillain-Barre syndrome.

Juvenile idiopathic inflammatory myositis (JIIM): The child can present with
inflammatory myositis without skin affection.

Investigations:
1. Elevated muscle enzymes (creatine kinase, AST, LDH and aldolase).
2. EMG changes suggestive of inflammatory myositis.
3. Muscle biopsy (usually not needed for diagnosis and can be replaced by MRI).

Treatment:
1. Corticosteroids: the mainstay of treatment.
2. Steroid-sparing agent: Methotrexate
3. Hydroxychloroquine: It reduces rash and maintains remission.
4. In severe cases: IV Immunoglobulins and Mycophenolate mofetil can be used.
5. Physical therapy and occupational therapy.

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Familial Mediterranean fever: FMF
It is the most common hereditary diseases known.

Definition: It is an auto-inflammatory disease and one of the periodic fever syndromes.

Etiology: It is an autosomal recessive disease, caused by MEFV gene located on chromosome

16.
It is common around the Mediterranean region among Jewish, Turkish and Arab.

Pathogenesis:
FMF mutations cause a defect in the pyrin protein of the innate immunity, causing unprovoked
inflammation. No autoantibodies are detected.

Clinical picture:
1. Recurrent attacks of fever, serositis (abdominal pain, chest pain + arthritis) and rash.
2. The attack lasts from 6 hours up to 1 week.
3. The patient can present by :
■ A picture resembling appendicitis. Arthritis is usually monoarticular, affecting large joints.
■ Erysipelas-like erythematous rash can occur on the ankle or the dorsum of the foot.

4. In-between the attacks, the patients are usually free of symptoms.

Complications: Amyloidosis in severe, untreated case.

Investigations:
Elevated acute phase reactants during the attacks.
Around 30% of patients experience elevated acute phase reactants in between attacks, despite
free of symptoms (subclinical inflammation).

Treatment
Prophylactic daily oral colchicine decreases the frequency, duration, and intensity of FMF flares. It
also prevents the development of systemic AA amyloidosis.

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Childhood Vasculitis
Childhood vasculitis includes a broad spectrum of diseases that have inflammation of the blood
vessels as a common pathophysiology.

Classification of Vasculitis:
1. Predominantly Large Vessel Vasculitis: Takayasu arteritis
2. Predominantly Medium Vessel Vasculitis: Childhood polyarteritis nodosa (PAN) and
Kawasaki disease
3. Predominantly Small Vessel Vasculitis: Wegener granulomatosis, Henoch-Schonlein
purpura
4. Other Vasculitides: Behcet disease, vasculitis secondary to infection (including hepatitis B-
associated polyarteritis nodosa), malignancies, drugs, and vasculitis associated with connective
tissue diseases.

Henoch-Schonlein Purpura (HSP)

It is the most common vasculitis of childhood and is characterized by immunoglobulin (Ig) A
deposition in the small vessels in the skin, joints, gastrointestinal tract, and kidney.

Age: Around 90% of HSP cases occur between the ages of 3 and 10 yr.

Etiology: The exact pathogenesis of HSP remains unknown. Given the seasonality of HSP
(common in winter and spring) and the frequency of preceding upper respiratory infections,
infectious triggers are suspected.

Clinical manifestations:
1. Skin: palpable purpura (in absence of coagulopathy and thrombocytopenia) is the hallmark
of the disease. It occurs in lower limbs and buttocks. Subcutaneous edema localized to the
dorsa of hands and feet is also common.
2. Arthritis: usually self-limiting and oligoarticular.
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3. GIT: including abdominal pain, vomiting, diarrhea, paralytic ileus and melena.
Intussusception is uncommon.
4. Renal: nephritis, hypertension or proteinuria.
5. Neurologic manifestations (intra-craniaI hemorrhage, seizures, and headache) can
occur due to hypertension or CNS vasculitis.

Diagnosis: On clinical basis (no specific lab finding).

Laboratory
1. Complete blood picture: normal platelet count
2. ESR, CRP : elevated (inflammation)
3. Urine analysis (screen for hematuria)
4. Stool analysis (screen for blood in stool)
5. Blood Urea, creatinine and C3: screen for nephritis
6. Ig A level (maybe elevated)
Imaging
1. X ray and abdominal and ultrasound if there is any doubt regarding gut perforation or
intussusception

Treatment:
1. Supportive in mild cases: e.g. Non-steroidal anti-inflammatory drugs.
2. Steroids (1 mg/kg/day for 1-2 weeks) reduce GIT and joint symptoms.

Kawasaki disease (KD)

Old name: mucocutaneous lymph node syndrome.
It is the leading cause of acquired heart disease in children in developed countries. It
commonly affects the coronaries.

Etiology: unknown (infectious trigger is suspected).

Age and gender: It is more common below 5 years of age and in boys.

Clinical criteria of classic Kawasaki (It needs high index of suspicion)

1- Fever persisting at least 5 days (38 degrees of more, unremitting).
2- Presence of at least 4 of 5 features:
a. Changes in extremities:
■ Acute: Erythema or edema of hands and feet.
■ Subacute: Periungual peeling of fingers and toes (weeks 2 and 3).
b. Polymorphous skin rash.
c. Bilateral bulbar conjunctival injection without exudate.
d. Changes in lips and oral cavity: erythema, lip cracking, strawberry tongue

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 e. Cervical lymphadenopathy (>1.5 cm diameter), usually unilateral.

3- Exclusion of other diseases with similar findings (see DP).

Cervical lymphadenopathy Skin rash

Other clinical features

1. Cardiovascular affection: coronary artery aneurysms, myocarditis.
2. Hepatic dysfunction.
3. Arthritis
4. CNS: extreme irritability
5. Perineal desquamation.

In atypical or incomplete KD, patients have persistent fever but fewer than 4 of the 5
characteristics. In these patients, laboratory and echocardiographic data can assist in the
diagnosis.

Laboratory Findings
1. Leukocytosis with neutrophilia, elevated ESR and CRP, hypoalbuminemia,
thrombocytosis after week 1
2. Sterile pyuria
3. Elevated serum transaminases and plasma lipids.

Differential diagnosis:
1. Viral infections: eg Measles, EBV, CMV, Enteroviruses.
2. Bacterial infections: eg Scarlet fever, Meningococcemia
3. Rheumatological disease: Systemic-onset JIA
4. Other: Drug-hypersensitivity reaction, Steven-Johnson syndrome.

Stages:
1. The acute febrile phase: fever and other acute signs of illness (1-2 weeks).
2. The subacute phase: desquamation, thrombocytosis, possibility of CAA (3 weeks).
3. The convalescent phase: when all clinical signs have disappeared and continues until
ESR returns to normal (6-8 weeks).

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Echocardiography should be performed at diagnosis and again after 2-3 weeks of illness. If the
results are normal, a repeat study should be performed 6-8 weeks after onset of illness.

Treatment of KD:
1. IV immunoglobulin 2 g/kg over 10-12 hours And Aspirin 80-100 mg/kg/day every 6
hours orally until patient is afebrile for at least 48 hours.
2. If no coronary affection: Aspirin 3-5 mg/kg once daily orally until 6-8 weeks after
illness onset.
3. If coronaries are affected: Long term anticoagulation and low-dose aspirin.

Sarcoidosis
Sarcoidosis is a rare granulomatous disease.

Pathology: Non- caseating granulomatous lesions. It can occur in any organ

(diagnostic).

Clinical picture: depending on age of onset

1. Blau syndrome: autosomal dominant, characterized by the early onset of
granulomatous inflammation involving the skin, eyes, and joints (triad of rash, uveitis
and arthritis).
2. Early-onset sarcoidosis (EOS): In children less than 4 years old. It is similar to Blau
syndrome, but not
familial.
3. Pediatric onset adult sarcoidosis: occurs in older children with systemic features
(fever, weight loss, malaise
lymphadenopathy.

Fine maculopapular
erythematous rash in a
child with Blau syndron

Investigations:
1. Anemia, leukopenia, and eosinophilia may be seen.
2. Angiotensin converting enzyme (ACE) may be elevated.

Treatment:
1. Corticosteroids: mainstay of treatment.
2. Steroid-sparing agents: methotrexate and leflunomide.
3. Biologic agents: Anti-TNF a (adalimumab) can be used.

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