Illustrated Baby Nelson Special Pediatrics Part2

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Dr Mohamed El Koumi
Consultant Pediatrics and Pediatric Nephrology
MD Pediatrics
Membership of Royal College of Pediatrics and Child Health
(MRCPCH; UK), (FRCPCH, UK)
IPNA Senior Clinical Fellow Pediatric Nephrology, Queen Elizabeth
Hospital, Glasgow, Scotland (UK)
Assistant professor of pediatrics

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Dr Ayman Azab
Professor of pediatrics and neonatology, National Research Center
Consultant neonatologist, Adan hospital, Kuwait
Dr Osama Taha Amer

Professor of pediatrics, Zagazig University
Consultant pediatric pulmonologist
.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬
Dr Laila Sherief ‫ﺩﻋﻮﺍﺗﻜﻢ‬ .‫ ﻣﺎﺟﺪ ﺍﻟﻤﻨﺼﻮﺭ‬.‫ﺭﻓﻌﻪ ﺩ‬
Professor of pediatrics, Zagazig University
14‫ﺍﻟﺪﻓﻌﺔ ﺍﻝ‬
Consultant pediatric hematology and oncology
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I was very blessed to issue this new edition of Illustrated Baby Nelson
with three pioneer figures in pediatrics and neonatology sharing their
thoughts, insights and relentless revision of neonatology, hematology
and pulmonology chapters. Hats off to Dr Ayman Azab, Dr Osama Taha
Amer, Dr Laila Sherief.
Thank you for the man for whom I myself and this book owe him so
much and without his support it would never come to light and
persist; Mr Sayed Mahmoud, founder of university book center.
Thanks to his soul that exist with and inspire us all
And finally I end my foreword with these lines to Richard Templer:
“Be prepared to be a little brave every day. If you don’t, you’ll grow
stagnant and mouldy. We all have a comfort zone where we feel safe
and warm and dry. But every now and then we need to step outside
and be challenged, be frightened, be stimulated. It’s this way that we
stay young and feel good about ourselves “
Richard Templer (The rules of life)
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‫ﺩﻋﻮﺍﺗﻜﻢ‬ ‫ﺭﻓﻌﻪ ﺩ‪ .‬ﻣﺎﺟﺪ ﺍﻟﻤﻨﺼﻮﺭ‪.‬‬
‫ﺍﻟﺪﻓﻌﺔ ﺍﻝ‪14‬‬
Page | 1
3 Illustrated Baby Nelson
List Of Abbreviations

Lt. V. : Left ventricle

Rt. V. : Right ventricle
Lt. A : Left atrium
Rt. A : Right atrium
LVH : Left ventricle hypertrophy.
RVH : Right ventricle hypertrophy
LAD : Left atrium dilatation
RAD : Right atrium dilatation
C.P. angle. : Cardiophernic angle
P.H+ : Pulmonary hypertension
S1 : First heart sound
S2 : Second heart sound
P2 : Pulmonary component of the second heart sound
A2 : Aortic component of the second heart sound.
RVF : Right ventricle failure.
LVF : Left ventricle failure
BVF : Biventricular failure
COP : Cardiac output
LPSB : Left parasternal border
CXR : Chest X-ray
SBE : Subacute bacterial endocarditis
RBBB : Right bundle branch block
VMA : Vallinyle mandilic acid
BVH : Biventricular hypertrophy.
PGE1 : Prostaglandin E1
PFO : Patent formen ovale.
TOF : Tetralogy of Fallot
DORV : Double outlet right ventricle

Page | 3 Illustrated Baby Nelson
Diagnosis of a cardiac patient

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n Pulmonary venous
congestion (PVC)

In infants In older child
- Poor feeding (dyspnea - Dyspnea; exertional and

on suckling) positional with or without

- Recurrent heart failure paroxysmal nocturnal

- Recurrent chest dyspnea

infections - Cough exertional & positional
- Hemoptysis
- Retarded growth

o Systemic venous p Low cardiac output

congestion (SVC) (LCOP)
symptoms

- Edema (dependent, bilateral , - Dizziness

pitting edema) - Easy fatigability
- Dyspepsia - Exertional syncopal attacks
- Abdominal pain (enlarged - Chest pain
tender liver) - Retarded growth

q Central Cyanosis

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Suspected congenital heart disease Suspected rheumatic heart disease

- Cyanosis (in lips & extremities) - Start with measuring blood pressure &
- Characteristic facies (e.g. Down) checking peripheral signs suggesting AR.
- Check patient’s weight and height - Check for edema in dyspneic patient
And plot on appropriate charts - Clubbing of fingers and toes and other
- Check blood pressure & pulse features suggesting infective endocarditis
- Clubbing of fingers and toes

Page | 4
Remember the following notes

A
* Most of the anterior surface
of the precordium is made
of right ventricle
* Left atrium does not appear

in anterior view
* Any chamber enlarges in

its longitudinal axis mainly
B
During systole; left ventricle
elongate to hit a localized area
of chest wall producing the
apex beat
C
* Right atrium depolarizes
first followed by left atrium
* Both ventricles depolarize
at the same time
* Ventricles depolarize from

inwards to outwards
D
* Pressures in the left side
exceed that in the right
* After birth pressures in the

Right side are slightly higher
than normal
* Pressure values increase

steadily with age

3
Step 3 : Precordial examination

Precordial examination includes inspection, palpation and percussion of the precordium. It detects basically cardiac chamber and or big artery enlargement
Precordial examination Chest X Ray ECG
Left ventricle
- Apex beat is shifted down and out
hypertrophy
- Apex beat is localized
(LVH) or
Apex shifts down & V1 Deep S V6 Tall R
Enlargement
out
Obtuse cardiophernic
angle
Right - Apex beat is shifted directly out

ventricle - Apex beat is diffuse
Apex shifts direct out
hypertrophy - Precordial bulge
(RVH) or - Left para sternal pulsation
Acute cardiophernic
Enlargement - Epigastric pulsation
Angle V1 Tall R V6 Deep S
Tall ,peaked P wave (P-pulmonale)

Right atrial
dilatation
Usually is not detectable clinically
(RAD) n Right cardiac shadow
wide and bifid P wave (P-mitrale)

Left atrial
Mitralization
dilatation
Usually is not detectable clinically Double
(LAD)
contour
2
Evidence of pulmonary artery dilatation in cases with pulmonary hypertension(PH)

- Palpation of the pulmonary area: Pulsating pulmonary area (normally silent area)
- Percussion of the pulmonary area: Dull (normally resonant area)
Feel the murmur i.e. Thrills (Thrill is a palpable murmur)
Value of detecting thrill
Definitely, there will be a murmur to be heard with the same timing of the thrill
This murmur is organic never functional or innocent
If the murmur is propagating ; the thrill usually is not propagating (i.e. localizing sign)
If thrill is detected; check where?
Mitral area (left 5th interspace)
Left parasternal border area(left 3rd and 4th interspaces)
Pulmonary area(left 2nd interspace)
Aortic area(right 2nd interspace)
Comment on the apex with (Remember SCART)
Normal apex Abnormal apex
th
Site Occupies the left 5 interspace, Shifted outward & downward (LVH)
midclavicular line Shifted direct outward (RVH)
Absent; impalpable
Character Normal intensity Hyperdynamic (strong and rapid )in volume overload e.g. MR, CM,AR
Heaving(strong and sustained) in pressure overload e.g. AS
Area Occupies one interspace Diffuse (apex beat occupies more than one interspace) in RVH
Rhythm Regular Irregular in irregular arrhythmias
Thrills Absent May be Present:
R Systolic thrill ( MR, CM,VSD)
R Diastolic thrill ( MS, CM )
MR: Mitral Regurge; CM: combined mitral lesion (previously double mitral);AR: Aortic Regurge; AS: Aortic stenosis; VSD: ventricular septal defect; MS: Mitral stenosis
3
Cardiac Cycle
Systole (duration: ) Diastole
S1 A2 P2
Isometric
Protodiastolic Isometric relaxation Atrial
1st heart sound contraction Ejection phase 2nd heart sound Filling phase
phase phase contraction phase
phase
- Due to closure - Ventricles - Intraventricular - Pressure in - Due to drop of - Ventricles continue - Blood flows from - Atria contract to
of the atrio contract pressure ventricles and intraventricular to relaxodecline atria to the push blood
ventricular without exceeds that in large arteries pressure at start of of intraventricular ventricles due to remaining in
valves at onset change in size big arteries o equalize o no diastoleo blood in pressure pressure the atria(40%)
of systole - Intraventricular semilunar net flow of big arteries try to gradient(60%)
- Amplitude pressure is valves open blood backflowo
depends on increasing semilunar valve ± 3rd heart ± 4th heart
amount of closure sound(vibration of sound(atrial
blood in - Amplitude depends myocardial muscle) contraction against
ventricles at on amount of blood N.B: stiff thickened
start of systole in large arteries at 3rd heart sound can be ventricle)
- Has 2 start of diastole heard in normal N.B:
components; - Has 2 components; infants as well as in 4th heart sound is
mitral & aortic & pulmonary congestive heart almost always
tricusped failure abnormal

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It is abnormal sound due to either blood flowing in an abnormal direction or blood flowing across narrow orifice (organic narrowing e.g. stenosis or relative)
Pressure gradient is required for murmur to develop
Murmurs are graded into 6 grades according to intensity and presence or absence of associated thrills(Grades 1-3 are without thrill and grades 4 - 6 with thrill)
Murmurs may be:
1. Organic: due to organic lesion in the heart either congenital or acquired
2. Relative: due to Ĺ blood flow through normal sized valve (soft, non propagating , without thrills and heart sound related is usually accentuated e.g. relative PS in PH)
3. Innocent murmur: heard over completely normal heart or great vessels. (soft, non propagating , without thrills, systolic, asymptomatic patient, normal heart sounds)
2
Step 4 : Auscultation
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1. First heart sound (S1) 2. Second heart sound (S2)
x Due to closure of Atrio ventricular valves at beginning of systole x Due to closure of semilunar valves at beginning of diastole
x Has 2 components oMitral :best heard over mitral area x Has 2 componentso Aortic ;best heard over aortic area
oTricusped : best heard over tricusped area o Pulmonary ;best heard over pulmonary area
x Muffled in oAtrio ventricular valves regurge x Muffled in : semilunar valve stenosis: o Aortic stenosis (pA2)
o Bradycardia oPulmonary stenosis (pP2)
x Accentuated in o Atrio ventricular valves stenosis x Accentuated in hypertension o Systemic hypertension (nA2)
oTachycardia o Pulmonary hypertension (nP2)
x S1 Splits in right and left Bundle branch block (BBB) x S2 Split : see below
Splitting of the second heart sound ( Detected by auscultating the pulmonary area)
Physiologic splitting Wide variable splitting Wide fixed splitting
The two components of S2(A2: aortic R S2 splits in whole respiratory cycle but R Wide splitting
component & P2:pulmonary component) wider splitting in inspiration R Does not vary with the respiratory cycle
usually splits in inspiration & unites in R Occur with prolonged or delayed right R Occurs with ASD
expiration ventricular systole
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S1 A2 P2
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2. Murmurs
1. Timing
Systolic Murmurs Diastolic Murmurs
Pan systolic Ejection systolic Early diastolic Mid diastolic
S1 S2 S1 S1 S2 S1 S1 S2 S1 S1 S2 S1
2. Site of Mitral area Left sternal Tricusped Aortic area Pulmonary Aortic areas Mitral area
maximum Border(3,4) area area
Intensity
Diagnosis MR VSD,ECD TR AS PS AR MS
Sounds p S1 p S1 p A2 p P2 n S1
Characters Blowing Harsh Blowing Harsh Harsh Soft Rumbling
Propagation Axilla Precordium Neck& Apex Sternal border Second aortic area Localized
ECD: Endocardial cushion defect; TR: tricuspid regurge; PS: pulmonary stenosis
N.B: Continuous (machinery or systolic/diastolic) murmurs: See later in PDA
Q2: Auscultatory findings in pulmonary hypertension(PH)?
1. Ejection systolic murmur over pulmonary area (with the relative murmur criteria)
2. Accentuated pulmonary component of the second heart sound
.B: pulmonary hypertension occur in cases with prolonged pulmonary congestion or prolonged increase pulmonary blood flow
Step 5 : Investigations
1. ECG and chest x ray: Help precordial examination in detecting cardiomegaly (ECG is invaluable for diagnosis of dysrhythmia and ischemia)
2. Echocardiography (& preoperative catheterization): Help auscultation establishing the final diagnosis
Value: - Describe lesions (site, size, intracardiac pressures, flow across the lesion and ventricular function).
- Detect complications e.g. Infective endocarditis, cardiomegaly
Page | 10
Congenital Heart Diseases (CHD)

Incidence
- 8 per 1000 live born infants have significant cardiac malformation
- The commonest CHD are VSD (30%), PDA (12%), and ASD (7%)
- About 10-15 % have complex lesions with more than one cardiac abnormality
Risk Factors
R Genetic predisposition suggested by family history of CHD
R Exposures during pregnancy e.g.
a. Drugs e.g. warfarin, anticonvulsants, alcohol
b. Diseases e.g. maternal rubella (o PDA), Maternal Diabetes Mellitus
R Chromosomal e.g.
a. Down syndrome o Atrio ventricular septal defect, VSD
b. Turner syndromeo Aortic stenosis, coarctation of aorta
c. Williams syndromeo Supra valvular aortic stenosis , pulmonary stenosis
a b c
Presentation
R Coincidental; accidental discovery of a murmur in an asymptomatic infant
R Cardiac failure /Cardiogenic shock e.g. in neonate ( critical aortic stenosis and
severe coarctation) or in infants(CHD with high pulmonary flow)
R Congestive pulmonary symptoms e.g. CHD with high pulmonary flow
R Cyanosis e.g. congenital cyanotic heart diseases
R Cardiomegaly detectable clinically or during routine chest radiograph
R Certain anatomic diagnosis may not be made by physical examination or chest
x ray or ECG alone ,so echocardiography is the mainstay of diagnostic imaging
R Recently
1. Antenatal fetal anomaly ultrasound screening
Can diagnose up to 70 % of significant lesions ,allowing earlier
diagnosis and planning of management
Important for any fetus with an increased risk e.g. Down syndrome
2. MRI allows 3 dimensional imaging of complex CHD, assessment of
hemodynamics, assists interventional cardiology and reduces the need for
cardiac catheterization. (Illustrated textbook of Paediatrics, Tom Lissauer)

Page | 11
Acyanotic Congenital Heart Diseases (ACHD)
ACHD constitutes 80% of all CHD

Classification
i. ACHD with left to right shunt (Potentially cyanotic CHD)
The commonest lesions in this category are
Ventricular septal defect (VSD)
Patent ductus arteriosus (PDA)
Atrial septal defect (ASD)
General clinical features
1. Degree of the left to right shunt, and 2. Manifestations of high pulmonary blood
consequently clinical manifestations is flow
dependent on: x Poor feeding (sweating and tachypnea)
R Size of the defect. in babies, exercise intolerance and easy
R Pressure gradient across the defect. fatigability in children
x Recurrent chest infections & chest
wheezes.
x Recurrent heart failure.
x Growth failure (faltering of growth)
3. Heart failure 4. Eisenmenger syndrome: Prolonged high

Usually GRHVQ¶WRFFXULQfull pulmonaU\EORRGIORZĺSXOPRQDU\
term neonates but can occur in K\SHUWHQVLRQGHYHORSVĺZLWKWLPHULJKWVLGH
infancy as pulmonary vascular KHDUWSUHVVXUHVH[FHHGVWKDWRIWKHOHIWĺ
pressure declines. UHYHUVDORIWKHVKXQWĺFHQWUDOF\DQRVLV
Risk is higher with large unrepaired defects
ii. ACHD without shunt
1. Obstructive lesions e.g. Aortic coarctation, Aortic stenosis, Pulmonary stenosis
Common clinical features:
1- Severe obstructive lesions can present early in life with heart failure.
2- Low cardiac output manifestations.
2. Non obstructive lesions e.g. Dextrocardia, Mitral valve prolapse

Page | 12

Ventricular septal defect (VSD)
Definition
Defect anywhere in the interventricular septum
Types of VSDs:
Inlet defect
Outlet defect; (also called

Perimembraneous defect: infundibular or sub
Adjacent to tricuspid valve arterial).
The commonest type (70%)
Muscular defects: Either
single or multiple (Swiss
cheese).
Hemodynamics

x Blood is shunted from the left ventricle(higher

pressure) to the right ventricle(lower pressure)
x Increased pulmonary blood flow
x Pulmonary congestive symptoms

x Volume overload over right ventricle ,left
atrium and left ventricle
Clinical picture
Small VSD Large VSD

General - Usually asymptomatic History
manifestations - Discovered accidentally x Breathlessness during suckling
x Recurrent chest infections
x Recurrent chest wheezes
Physical
x Breathlessness ,tachypnea,
tachycardia and enlarged tender liver
(heart failure)
x Faltering of growth

Page | 13
Small VSD Large VSD

Precordial - Systolic thrill over the lower left sternal border
Examination - Biventricular enlargement by 2 months
of age
- Active precordium
Auscultation x Murmur of VSD x Murmur of VSD
- Pansystolic. Same but softer
- On lower left sternal border. x Pulmonary area: Accentuated P2 &
- Propagate all over the heart. soft systolic murmur indicates
- Harsh ; loud . pulmonary hypertension.
x Apical
Short rumbling mid diastolic murmur
Produced by the increased volume of
blood flow across the mitral valve
Usually indicates a Pulmonary-to-
systemic blood flow ratio ratio of at
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Complications x Infective endocarditis x Heart failure
x Infective endocarditis
x Higher risk of Eisenmenger syndrome
Investigations
*Chest X-ray - Normal - Cardiomegaly with biventricular
enlargement & plethoric lungs.
* ECG - Normal - Biventricular enlargement (LVH and RVH
* Echo - Diagnostic (size smaller than - Diagnostic
aortic in diameter ;up to 3mm)
* Catheter - - Pre operative / interventional
Treatment
1. Small defect
- Avoid infective endocarditis by dental hygiene and antibiotic prophylaxis.
- Reassurance ; ( surgical intervention is not usually recommended)
- Follow up with ECG & Echo to confirm spontaneous closure

Page | 14

2. Large defect
A. Medical
- Control heart failure (Diuretics, Captopril).
- Antibiotics for chest infections
- Additional calorie input and monitor growth
- Avoid infective endocarditis
- Follow up with ECG & Echo to confirm spontaneous closure.
B. Surgical
Types
i- Palliative: Pulmonary artery banding reduce pulmonary blood flow
ii- Direct closure of the defect
Indications
i- Symptomatic large defects with uncontrollable heart failure or Growth
failure
ii- Progressive pulmonary hypertension.
Timing: at 3-6 months of life.
(Illustrated textbook of Paediatrics, Tom Lissauer)
Prognosis
30-50% of small defects (especially muscular) close spontaneously within the
first 2-years of life

Page | 15
Atrial Septal Defect (ASD)
Definition: Defect in the inter-atrial septum.
Types of ASD
R Secundum ASD
R Primum ASD (Partial atrio ventricular septal defect)
R Sinus venosus defect:
- Lies in the upper part of the septum near orifice of superior vena cava.
- Association: usually with partial anomalous pulmonary venous return
Secundum ASD Primum ASD

x The commonest type (80% of ASD) x Less common
x Lies in the middle part of the septum x Lies in the lower part of the septum
x Association x Association
May be with Holt Oram syndrome Usually associated with cleft of
(Absent radii, 1st degree heart block, mitral valve leafleto mitral
secundum ASD). regurge.
Hemodynamics
Blood is shunted from left atrium to right atrium o right ventricle oĹ
pulmonary blood flow ( more with primum ASD)
General manifestations
x Asymptomatic in most cases unless x Features of increased pulmonary
large ASDo features of increased blood flow in infancy including
pulmonary blood flow recurrent chest infections & heart
x Arrhythmias (4th decade onwards) failure.
Precordial Examination
- Usually normal (may be RVH) - Cardiomegaly with BVH

Page | 16
Auscultation
Pulmonary area Pulmonary area
Murmur of a relative pulmonary stenosis: Wide fixed splitting of S2
- Soft ejection systolic without thrill Wide splitting due to large filling of
- With accentuated P2 right ventricle
Fixed (does not vary with respiration)
due to constantfilling of right ventricle
in all phases of respiration
Apex Lower left sternal border

Pansystolic murmur of mitral regurge A short, rumbling mid-diastolic murmur
propagating to axilla in Primum ASD Produced by the increased volume of
blood flow across the tricuspid valve
Usually indicates a Pulmonary-to-
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Complications
Very rare; more common with primum ASD:
- Recurrent heart failure may occur with large defects.
- Recurrent pulmonary infections
- Infective endocarditis is extremely rare (can occur in primum defects)
- Reversal of the shunt may occur very late; in adulthood, by the 3rd - 4th decade.
Investigations
1. Chest X-ray
- Cardiomegaly with RVH & RAD.
- BVH in ostium primum defect
- Plethoric lungs (Ĺ pulmonary vascular markings)

Page | 17
2. ECG:
- RVH & RAD.( BVH in primum ASD)
- Right bundle branch block is common.
3. Echocardiography is diagnostic
4. Cardiac catheter: - Pre operative/corrective intervention
Treatment
1. Medical
x Same lines as for VSD
x Infective endocarditis prophylaxis is needed only for primum ASD with
mitral regurge
2. Surgical or transcatheter device closure is advised for
x All symptomatic patients
x Asymptomatic patLHQWVZLWKD4Sௗௗ4VUDWLR
RIDWOHDVWௗௗ
x Those with right ventricular enlargement
(Chest x ray after ASD device closure, source: Radiopaedia.com)
Prognosis
40% of secundum ASD defects close in 1st four years of life spontaneously

Page | 18
Patent ductus arteriosus (PDA)
Definition: Persistent fetal duct connecting the aorta & the pulmonary artery.
Connections
R The aortic end is just distal to left subclavian artery.
R Pulmonary end is at the bifurcation.
Association: Congenital rubella syndrome & prematures
Hemodynamics
R Blood is shunted from the higher pressure of aorta to
pulmonary artery o nn Pulmonary blood flow
R Run off of blood from Aorta to the pulmonary artery
mainly during diastole o lower diastolic pressure o
Hyperdynamic circulation
General Manifestations
1. Small duct 2. Big duct
R Asymptomatic ; discovered R Symptoms of increased

accidentally pulmonary blood flow (see before)
R Hyperdynamic circulation e.g. big
pulse pressure
Precordial examination Precordial examination
R Systolic thrill over the upper R Systolic thrill over the upper left
left sternal border sternal border
R Evidence of LVH
Auscultation
Left infraclavicular area
Continuous; machinery murmur (Gibson
murmur); Murmur may be systolic if the
diastolic component is masked:
1. Early in life (due to physiologically raised
pulmonary pressure) Apex
2. Very large defects (due to higher x A short, rumbling mid-diastolic murmur
pulmonary pressure) x Produced by the increased volume of blood
3. Pulmonary hypertension flow across the mitral valve in big defects

Page | 19

Investigations
1. Chest X ray and ECG
x 6PDOODV\PSWRPDWLF3'$ĺBoth are normal
x Large and symptomatic PDA ĺIndistinguishable from large VSD
Chest X-ray: Cardiomegaly and Plethoric lungs.
ECG: ĺLeft ventricle hypertrophy with large left to right shunt
ĺRight ventricle hypertrophy with pulmonary hypertension
2. Echocardiography is readily diagnostic
Complications
- As in large VSD plus Aneurismal dilatation and rupture of the duct
Treatment
A. Medical
- Control heart failure & prevent infective endocarditis (Infective endarteritis)
- Medical closure in preterm by I.V. indomethacin in the 1st week of life .
B. Transcatheter or Surgical closure
Irrespective of age, size or symptoms ,all PDAs should be closed, preferably
before 1 yr of age.
x Small PDAs are closed x Moderate to large PDAs are closed
with intravascular coils with an umbrella-like device
Differential diagnosis of continuous murmurs:

x An aorticopulmonary window defect
x A sinus of Valsalva aneurysm that has ruptured into the right side of the heart
or pulmonary artery, Coronary arteriovenous fistulas
x Truncus arteriosus
x VSD with aortic insufficiency, and combined aortic and mitral insufficiency
(to-and-fro murmur rather than continuous nature)

Page | 20
Atrio ventricular septal defect (AVSD)

(Endocardial cushion defect; ECD)
Definition
Defect in atrioventricular septum; complete defect is composed of:
1- Large ASD
2- Common & incompetent atrio ventricular valve.
3- Large VSD.
Association: common with Down syndrome.
Manifestations
- Features of increased pulmonary blood flow and intractable heart failure
develop early in infancy.
- Evidence of cardiomegaly and hyperactive precordium (RVH mainly)
- Systolic thrill on lower left sternal border.
Auscultation
1- Lower left sternal borderoPansystolic murmur
propagating all over the precordium
2- Pulmonary areao Systolic murmur of a relative
pulmonary stenosis or pulmonary hypertension
Clinical picture is very similar to large VSD and

cases are only diagnosable by Echocardiography
Treatment
1. Medical: - As for large VSD
2. Surgical
x Because of the risk of pulmonary vascular disease developing as early as
6-12 mo of age, Early surgical repair is mandatory to avoid early
pulmonary hypertension and intractable heart failure
x Complication :surgically induced heart block requiring placement of a
permanent pacemaker
x Pulmonary artery banding is an option as a palliative surgery

Page | 21
Coarctation of Aorta (CoA)
Constriction of the aorta to anywhere from aortic arch to aortic bifurcation.

Types
Ductal CoA: adjacent to ductus arteriosus; below origin of left subclavian artery
Preductal or postductal CoA : far uncommon
Association: Turner syndrome, Bicuspid aortic valve
1. Hypertension proximal to the

CoA (head
& upper limbs)
2. Collaterals
develop between
the proximal &
distal aortae
3. Hypotension distal to the CoA

(lower body & lower limbs)
4. In severe coarctation , blood is shunted from the pulmonary artery

to the descending aorta via a patent arterial ductus with subsequent:
x Perfusion of the lower body is dependent on the patent
ductus(duct dependent systemic flow)
x May be differential cyanosis (lower limbs blue, upper limbs
pink).
Clinical Picture
1. Severe coarctation
R Usually no symptoms are apparent at birth, but can develop within a week of
birth with the closure of the ductus arteriosus
R Presentation: poor feeding, congestive heart failure, cardiomegaly and
acidosis
2. Milder cases: Usually asymptomatic; may present in older child or adult with:
x Pulse
Bounding in upper limbs and carotids , weak or absent in lower limbs
Femoral pulse is delayed than radial pulse (unlike normal).
x Blood pressure :Higher in upper limbs than lower limb(unlike normal)
The upper-to-lower extremity pressure gradient will increase with exercise

Page | 22
x Murmur
R Systolic murmur with ejection click
R Over the base of the heart
R Transmitted to the left infrascapular area
In older patients with well-

developed collaterals:
A continuous murmur may
be heard over chest laterally
and posteriorly
3. Complicated cases: May present with:

* Systemic hypertension due to renal hypoperfusion.
* Intracranial hemorrhage due to hypertension or associated aneurysm of circle of
Willis.
Investigations
1- Chest X-ray:
x Cardiomegaly ( LVH )
x Notching of the inferior border of the ribs from
pressure erosion by enlarged collaterals is
common by late childhood(Rosler sign)
2- ECG: - LVH in older patients

3- Echocardiography is Diagnostic
4- When echocardiogram is equivocal: cardiac CT ,
MRI and catheter are alternative diagnostics
Treatment
1. In neonates with severe coarctation of the aorta
Infusion of prostaglandin E1 to reopen the ductus and re-establish
adequate lower extremity blood flow.
Once a diagnosis has been confirmed and the patient is stabilized, surgical
repair should be performed
2. Older cases require:
Control of hypertension and prophylaxis against infective endocarditis.
Surgical repair

Page | 23
Cyanotic Congenital Heart Disease (CCHD)
Classification
CCHD with decreased pulmonary CCHD with increased pulmonary

blood flow blood flow
With RVH With RVH
- Fallot tetralogy - Transposition of great arteries (TGA)
- Pulmonary atresia with VSD - Total anomalous pulmonary venous return
With LVH - Eisenmenger Syndrome
- Tricusped atresia With BVH
- Ebstein anomaly - Truncus arteriosus
- Pulmonary atresia with VSD - Single ventricle
Criteria
- Hypercyanotic spells (attacks of - Poor feeding “dyspnea on suckling”.
increasing cyanosis) - Recurrent chest infections is common
- Heart failure is very rare - Recurrent heart failure is common
- P2 (pulmonary component of S2) o p - P2 o n
- Chest X-ray o lung oligaemia - Chest X-ray o plethora.
- Growth retardation occurs in long standing, symptomatic, uncorrected lesions.
Central cyanosis
Definition
Bluish discoloration of skin and mucous membranes due to presence of > 5 gm /ml
reduced hemoglobin in the capillary blood.
Causes
1. Congenital heart diseases are the main cause of chronic central cyanosis
- The commonest cyanotic congenital heart disease is Fallot tetralogy.
- The commonest cyanotic congenital heart disease presenting at birth is TGA.
2. Respiratory failure (usually acute cyanosis)
Presentation
- Early it may be overlooked and become evident only during crying and feeding
- Then it becomes apparent at rest; noted mainly in inner lips and tongue
Consequences
- Cyanotic clubbing, dusky blue skin, gray sclerae with engorged blood vessels
- Polycythemia
- Increased risk of Relative iron deficiency and Cerebral stroke

Page | 24

CCHD with decreased pulmonary blood flow
Fallot Tetralogy
Definition
Commonest cyanotic congenital heart disease with decreased pulmonary blood
flow ; Composed of

Aortic dextroposition
Aorta overrides the
ventricular septal defect
Receives mixed blood
Pulmonary stenosis
Mainly infundibular
(muscular) but may be
valvular VSD
Usually large
Right ventricle hypertrophy Lies just below the
Usually mild RVH aortic valve
Due to right ventricle
out flow obstruction
Hemodynamics
A. Degree of pulmonary stenosis (PS) determines degree of right to left shunt:
1. Severe PS
R Early right to left shunt o cyanosis appear in the neonatal period
R Pulmonary blood flow is mainly dependent on flow through the ductus
arteriosus
R When the ductus begins to close in the 1st few hours or days of life,
severe cyanosis and circulatory collapse may occur
2. Mild to moderate PS
Patient is initially pink; over time, pulmonary stenosis gradually
increases o right to left shunting o cyanosis appear within months
B. Pulmonary blood flow is maintained
R In neonate via ductus arteriosus
R In older child via Multiple aortopulmonary collateral arteries arising
from the ascending and descending aorta

Page | 25
Clinical picture
1. Central Cyanosis
R Often, cyanosis is not present at birth; but with
increasing hypertrophy of the right ventricular
infundibulum as the patient grows, cyanosis occurs
later in the 1st yearr of life
R Infants with severe degrees of PS, neonatal
cyanosis is noted immediately
R Infants with mild degrees of PS may initially be
seen with heart failure caused by a ventricular-level
left-to-right shunt
R Cases who aren’t initially visibly cyanotic are
termed Acyanotic or pink Fallot .
2. Cyanotic Clubbing of fingers and toes
3. Growth retardation (Stunting) in unrepaired cases
4. Squatting position
R Older children ,with significant cyanosis at rest, have
dyspnea on exertion
R After physical effort o dyspnea increases o the child
assumes squatting position for the relief of dyspnea
R Theory: Squatting okink of femoral arteries on systemic
vascular resistance on aortic pressure on pulmonary blood
flow on blood oxygenation.
5. Paroxysmal hypercyanotic Spells (Hypoxic, “blue,” or “tet” spells)
Incidence
Mainly in the 1st 2 years of life; triggered by crying, feeding or infection
Mechanism
Infundibular spasm o reduction of an already reduced pulmonary blood
flowo if prolongedo severe systemic hypoxia and metabolic acidosis
Clinically
Increasing cyanosis
Respiratory distress Irritability and restless
Decreasing murmur intensity
Spell lasts from a few minutes to a few hours

Severe spell may lead to convulsions, cerebrovascular stroke or even death

Page | 26
6. Cardiac examination
Precordial
- Normal heart size (may be mild RVH)
- Systolic thrill over left sternal border.
Auscultation
- S2: single (A2 only is heard)
- Murmur: systolic (organic PS) on the upper and mid left sternal border.
Investigations
1. Chest X-ray
Coeur en sabot or boot
shaped heart
Narrow base
Oligaemic lung Exaggerated waist
fields Rounded uplifted apex
- Heart size is normal or
mild RVH
2. Echocardiography
Two-dimensional
Echo is Diagnostic
3. Others
- ECG shows RVH
- Catheter o Pre-operative
- CBC show polycythemia
Complications
Early corrective surgery in infancy made it rare
1. Polycythaemia due to
R Hypoxemia o n erythropiotine o polycythaemia
R Relative iron deficiency increase polycythaemia
2. Cerebral thrombosis due to:
R Extreme polycythemia o sluggish blood flow
R Microcytosis due to relative iron deficiency origid
non deformable RBCs
3. Brain abscess due to septic emboli and lack of pulmonary
filtration

Page | 27
4. Pulmonary tuberculosis 6. Heart failure is rare; may

due to pulmonary be iatrogenic with big
oligaemia shunt
5. Infective endocarditis 7. Associated anomalies e.g.

DiGeorge syndrome or
CATCH 22 (cardiac
defects, abnormal facies,
thymic hypoplasia, cleft
palate, hypocalcemia).
Treatment
1. Medical
A. Treatment of hypoxic spells (in sequence)
R Don’t Panic
R Calm and hold the infant in Knee-chest (frog) position
± pressure to femoral pulses.
R Facial oxygen (if not distressing the child)
R Avoid premature attempts to obtain blood samples to
avoid further agitation
R Morphine 0.1mg/kg SC/IM/IV

Suppress the respiratory center
Caution in infants less than 3 months of age
R Fluid bolus 10ml/kg of NaCl 0.9% or Colloid IV
R Sodium bicarbonate 1mEq/kg IV (= 1ml/kg of 8.4%)
R Improve right ventricle out flow and reduce right to left shunt by either:
i. Propranolol 0.1mg/kg IV over 5 minutes.
Value : Reduces infundibular spasm
Contraindicated if already on maximal dose of oral beta blockers.
OR
ii. Phenylephrine 5-10mcg/kg (slow IV push)
Value: Increases systemic vascular resistance
R PICU Intervention : Intubation and ventilation for spells resistant to the

above management

Page | 28
x After the spell is over:

Oral propranolol prophylaxis 0.5-1 mg/kg/6hours
Avoid digitalis as it may induce infundibular spasm
Arrange for surgery
B. Avoid cerebral thrombosis by
x Treatment of relative iron deficiency
x For severe polycythemia
Adequate hydration
Phlebotomy
Partial exchange transfusion with albumin or saline.
C. Prophylaxis & treatment of infective endocarditis.
2. Surgical
Indicated as soon as the spells begin
A. Palliative shunts
* Idea: Anastomosis between aorta and pulmonary artery to allow n pulmonary
blood flow
* Modified Blalock Taussig operation:
Anastomosis between subclavian artery & ipsilateral pulmonary artery using
Gore Tex conduit (Potts and Waterston operations are obsolete)
B. Total repair:
Can be done between 4 months to 2 years according to severity and available
cardiac center

Page | 29
Other causes of CCHD with decreased pulmonary blood flow

All are Fallot tet. like in clinical presentation and management
Differentiated from Fallot tet by Echocardiography and diagnostic catheter
Ebstein's Anomaly
Composed of
Huge right atrium
Downward displacement of tricusped valve leaflets.
Tricusped regurge is common.
Small right ventricle
Clinically
May be asymptomatic
Splitting of S1 and S2
May be
Mild cyanosis
Atrial arrythmias
Pansystolic murmer (tricusped regurge)
May be heart failure.
Chest X-ray: May be huge cardiomegaly in.
ECG o Right bundle branch block (RBBB) and RAD

Echocardiography and color Doppler : diagnostic
RV
Huge
RA
LV
RV

2
3. Pulmonary atresia 4. Tricusped atresia

With VSD Without VSD
x Blood in right. ventricle pass to left

ventricle via VSD so, Left ventricle x Blood in right atrium pass via patent x Atretic tricusped valve o Blood in right atrium pass
contain mixed Blood o cyanosis. foramen ovale (PFO) o left atrium via PFO o left atrium o left ventricle o cyanosis.
x Pulmonary blood flow depends on PDA o left ventricle o cyanosis. x Pulmonary blood flow is dependent on VSD or PDA.
or collaterals between Aorta & x PFO & PDA are essential for life. x Right ventricle is hypoplastic.
pulmonary artery.
Presentation
- Cyanosis is evident at birth o increase in intensity with ductus arteriosus closure.
- Single second heart sound (only A2 is heard).
- No murmurs. (may be machinery of PDA or collaterals). - Murmur of VSD (± PDA).

Diagnosis
- Echocardiography can differentiate it from Fallot tetralogy.
Treatment
- Once suspected after birth: PGE1 infusion to keep the ductus open
- Operative: Palliative shunts/ Total correction
- Medical: measures for polycythemia and infective endocarditis(as before)
Page | 31
CCHD with increased pulmonary blood flow

1. Transposition of Great arteries (TGA)
Description
3. Mixing of blood
occur via PFO, 2. Pulmonary artery arise
VSD or PDA from left ventricle
1. Aorta arise from
right ventricle
Incidence: Common in infant of diabetic mother.
Types: - Isolated TGA

- TGA With VSD
- TGA With VSD and pulmonary stenosis
- Corrected TGA
Isolated (intact ventricular septum) TGA With VSD
Medical emergency
* Severe cyanosis at birth - Milder cyanosis
* With ductus closure o marked cyanosis with - Manifestations of increased
acidosis and hypoglycemia pulmonary blood flow
* No murmur - VSD murmur.
* Single accentuated S2 (anteriorly placed aorta)

Page | 32
Investigations
Chest x ray
Cardiomegaly (egg on side)
Plethoric lung
ECG: RVH.
Echo.: Diagnostic
Cardiac catheter: Preoperative
Treatment
1- Maintain PDA o PGE1 infusion & avoid O2. - Treatment of heart
2- Palliative operation: Rashkind balloon atrial failure (3D).
septostomy o create large ASD o free intra
cardiac mixing.
3- Total correction: either
- Arterial switch operation (anatomical - Arterial switch operation
correction)
- Atrial switch operation.
4- Other lines of treatment: - Avoid cerebral thrombosis (see Fallot tet)
- Precautions against infective endocarditis
2. Total anomalous pulmonary venous return (TAPVR)

x Pulmonary veins drain into right side of the heart either:
- In superior vena cava ( supra cardiac)
- In coronary sinus (cardiac)
- In inferior vena cava (infra cardiac)
x ASD allow blood in right atrium to pass to left atrium
o blood mixing o cyanosis.
x Chest X-ray
Snowman in snowstorm or
Figure 8 shaped heart.
x Echo is diagnostic

Page | 33
3. Truncus arteriosus (TA)

Description
2. One semilunar valve

1. One arterial trunk leave (Truncal valve)
the heart giving rise to
both aorta & pulmonary 3. Large VSD below the
artery trunk
Types
Type I Type II Type III Type IV

“pseudo truncus”
Single pulmonary Two pulmonary Two pulmonary Arteries arising

artery from left. arteries from the arteries from the from the
Side posterior wall lateral wall descending aorta o
supply the lungs.
Clinical picture
- Cyanosis o variable onset (usually minimal esp. in neonate & infants).
- Features of increased pulmonary blood flow
- S2 o single.
- VSD murmur.
- Chest X-ray o Right sided aortic arch in 50% of cases.
Treatment
1. Treatment of heart failure.
2. Surgical correction.
4. Single ventricle
- Absent interventricular septum o both Aorta & pulmonary artery arise from
common ventricle o free mixing of blood o cyanosis.
- Degree of cyanosis depends on whether pulmonary valve is stenotic or not which
determine pulmonary blood flow.

Page | 34

Valvular lesions
1. Mitral Stenosis (MS)
Causes
1- Rheumatic (mainly)
2- Congenital (rarely)
Hemodynamics
R MS o Blood accumulate in left atrium o left atrial dilatation
o pulmonary congestion and pulmonary congestive symptoms
R Prolonged pulmonary congestion o pulmonary hypertension with low cardiac
output symptoms
R Prolonged pulmonary hypertension oRight ventricular hypertrophy & right
ventricle failureo systemic congestive symptoms
Symptoms
x Mild cases may be asymptomatic ; discovered accidentally
x Pulmonary venous congestive manifestations with or without systemic venous
congestive manifestations.
Precordial examination
1. Weak apex beat; Slapping apex due to palpable first heart sound.
2. Pulmonary pulsation (palpable second heart sound) and dull pulmonary area in
cases with pulmonary hypertension.
Auscultation
Pulmonary area (in cases with
pulmonary hypertension):
- Accentuated S2.
- Ejection systolic murmur
Apex
Accentuated S1
Opening snap
Murmur: localized mid diastolic rumbling
with pre systolic accentuation

Page | 35
Complications
* Valve - Rheumatic activity
- Bacterial endocarditis
- Calcification
* Left atrium - Dilatationo compression manifestations
- Dysrhythmias
- Intra atrial thrombi
* Ventricle - Right ventricular failure
2. Aortic Regurge (AR)
Causes
2- Syphilitic, Marfan syndrome or post-operative (rare).
Hemodynamics
1- Incompetent aortic valve o In diastole blood returns to the heart leading to:
- Decreased diastolic pressure.
- Large end diastolic volume of left ventricle o increased systolic
pressure.
2- High systolic pressure and low diastolic pressure result in hyperdynamic
circulation.
Symptoms
1- Manifestations of low cardiac output.
2- Palpitation with exertion.
General examination: (peripheral signs suggesting A.R.)
1. Corrigan sign = visible arterial pulsations in carotid arteries.
2. De Musset sign = head nodding with each heartbeat.
3. Wide pulse pressure.
4. Water hammer pulse.
5. Capillary pulsations (in nail beds and lips).
6. Hill’s sign: Lower limb’s systolic pressure is higher than upper limb by > 20
mmHg.
7. Pistol shot due to push of blood in an empty artery.
8. Duroisier sign: diastolic murmur on pressing femoral artery by distal edge of
stethoscope.
- Hyper dynamic apex (forcible, non-sustained).
- Left ventricular enlargement (LVH).

Page | 36
Auscultation
Aortic area
1. Early diastolic murmur
R On the 1st & 2nd aortic areas
R Increases by leaning forward & in expiration
R Propagates to the apex
2. May be ejection systolic murmur due to functional aortic stenosis
3. Mitral regurge (MR)

Causes
2- Congenital (rarely)
3- Mitral valve prolapse
Hemodynamics
1- Incompetent mitral valve o in systole blood returns to the left atrium o left
atrial dilatation and pulmonary congestion o pulmonary hypertension.
2- Large end diastolic volume of left ventricle o left ventricle enlargement.
Symptoms
- May be asymptomatic in early cases
- Palpitation with exertion.
- Pulmonary venous congestive manifestations.
- Hyper dynamic apex. (forcible, non-sustained).
- May be apical systolic thrill.
- May be evidence of pulmonary hypertension(dull, pulsating pulmonary area)
Auscultation
1. Apex
- Muffled S1.
- Murmur o Pansystolic.
o Propagates to the axilla
2. Pulmonary area
In cases with pulmonary hypertension:
- Accentuated S2.
- Ejection systolic murmur.

Page | 37
Aortic stenosis (AS)

Causes
1. Rheumatic 2. Congenital
Valvular stenosis a. Valvular: bicusped aortic valve
- The commonest b. Subvalvular: a membrane or septal hyperterophy
- About 70% (hypertrophic obstructive cardiomyopathy
c. Supravalvular (With Williams syndrome : Elfin facies,
hypercalcemia, Cocktail party chatter).
Hemodynamics
- Left ventricle outflow obstruction
o Low cardiac output.
o Left ventricle hypertrophy & left ventricle failure.
Symptoms
1. Critical stenosis can present early in life with heart failure
2. Milder cases
May be asymptomatic
Manifestations of low cardiac output in older child.
Manifestations of complications
- Heaving apex (forcible, sustained).
- Systolic thrill over aortic area and the neck.
Auscultation
Aortic area: - Muffled, delayed aortic component of S2.
- Murmur o Harsh ejection systolic murmur
o Best heard on 1st aortic area
o Propagate to the neck & the apex.
Complications
1. Left ventricular failure
2. Bacterial endocarditis
3. Sudden cardiac death
Treatment
R Medical
- Exercise restriction for severe stenosis
- Prophylaxis against endocarditis
- Avoid vasodilators
R Interventional / surgical (Balloon valvoplasty or valvotomy or valve replacement)
For: Symptomatic cases and/ or Pressure gradient across the valve > 40mmHg

Page | 38
Pulmonary stenosis (PS)
Causes
- Congenital mainly.
Symptoms
1- Asymptomatic in mild cases
2- Severe obstructive lesions can present early in life with heart failure.
3- Manifestations of low cardiac output in older child.
- Right ventricular enlargement (RVH).
- Systolic thrill over pulmonary area.
Auscultation
Pulmonary area
Muffled pulmonary component of S2.
Murmur o Ejection systolic on pulmonary area propagate to the left
parasternal area.
Investigations of valvular lesions
Investigations Value
Chest x ray - Detect cardiomegaly
- Pulmonary vascular markings:
- Oligemic in pulmonary stenosis
- Prominent in left sided failure
- Specific configuration
ECG - Detect chamber enlargement
- Myocardial ischemia
Echocardiography - Diagnostic ; see before
Catheterization - Diagnostic ; done pre-operative
- Interventional
Treatment of valvular lesions

A. Medical
1. Afterload reducers e.g. captopril for regurgitant lesions.
2. Exercise restriction for severe stenotic lesions.
3. Treat complications:
- Heart failure
- Infective endocarditis.
- Arrythmias

Page | 39
4- Prophylaxis against
- Infective endocarditis.
- Rheumatic fever (in rheumatic cases).
B. Interventional
Balloon valvoplasty for symptomatic, non-calcific, stenotic lesions e.g.
- AS
- PS
- MS
C. Surgical
1- Valvotomy for stenosis
2- Valve repair for regurge
3- Valve replacement.

Page | 40
Acute Rheumatic Fever (ARF)
Definition
Immunologic disease affecting mainly the heart and joints& less frequently central
nervous system, skin and subcutaneous tissue
Risk factors
R Peak of onset between 5-15 year (rare before 5 years)
R Genetic predisposition
R Moderate and High risk populations : Developing countries
R Low risk populations : USA, Canada, western Europe
Pathogenesis
Group A Streptococcal (GAS) pharyngitis (M serotypes 1, 3, 5, 6,18, 24)
Antibodies formed against Streptococcal infection alter

streptococcal cross react host connective tissue
against host connective tissue antigenicity
Inflammation
Proliferative with Aschoff Exudative (in joints) with

nodules as in the heart and inflammatory edema o
subcutaneous nodules resolve without residual
Valvulitis due to endocardial inflammation may destroy

valves resulting in valve regurge (in acute stage) OR end up
in valve fibrosis and stenosis OR a mix of both

Page | 41
Clinical Picture
A latent period of 1-3 weeks usually exist between pharyngitis and clinical
symptoms of acute rheumatic fever
Major Criteria of Rheumatic Fever
1. Arthritis
R The commonest presenting sign 75%
R Distribution
Usually affect big joints (e.g. knee, ankles, wrist, elbow).
Polyarticular arthritis; either simultaneous or successive.
Migratory arthitis oFleet form one joint to another.
R Joint examination
Inspectiono Red ,hot ,swollen (inflamed)
Passive movementoSeverely tender
Active movemento Absolute limitation of movement
R Course :
Dramatic response to salicylates within 48 hours.
Resolve without residuals, even without treatment, over one week.
R Arthritis now refers to polyarthritis in low-risk populations, but to monoarthritis or
polyarthralgia in moderate/high-risk populations
2. Carditis
R The 2nd common(50%) and most serious manifestation of ARF
R Pancarditiso inflammation of endocarium,myocardium and pericardium
R Carditis may be silent or late onset appearing after 6 weeks – 6 months
R Carditis is now defined as clinical and/or subclinical (echocardiographic valvulitis)
i. Endocarditis: Valvulitis
Affect commonly the mitral valve with or without aortic valve:
a. Mitral valve
Valve edema o transient mitral stenosis o mid diastolic rumbling
murmur (Carey Combs murmur)
Valve destruction o mitral regurge o apical holosystolic murmur
propagating to the axilla with muffled 1st heart sound.
b. Aortic valve
Aortic regurgeo left sternal border
early diastolic murmur.

Page | 42
2. Myocarditis
R Tachycardia out of proportion to age & fever(rarely bradycardia due to heart
block)
R Heart failure indicates severe carditis with
Marked dyspnea
Enlarged tender liver
Gallop rhythm, muffled heart sounds
Cardiomegaly
3. Pericarditis
a. Dry pericarditis b. Pericardial effusion

Stitching chest pain Dull aching pain.
Pericardial rub (on the bare area of Distant heart sounds.
the heart, unrelated to respiration).
Investigations for carditis

ECG may show Low voltage ECG in pericardial effusion.
Chest x ray may show cardiomegaly
Echocardiographic findings include mitral and/or aortic regurgitation,
pericardial effusion, and decreased ventricular contractility
3. Rheumatic chorea “Sydnham Chorea” (10%)

Incidence
More in girls 8-12 years (school age).
Occur weeks or months after pharyngitis so, other criteria are usually
lacking.
May coexist with other rheumatic fever manifestations in 10%
Due to: Dysfunction of the basal ganglia.
Manifestations
1. Emotional lability and personality changes
2. Involuntary movements
Sudden ,jerky ,spontaneous pseudo purposeful movements of limbs
Facial grimace.
Distribution: Proximal more than distal.
Increase with emotional stress and decrease by sleep.
3. Hypotonia

Page | 43
Tests for rheumatic chorea

Cannot maintain arms extended o spooning &
pronation of hands (Choreic hand).
Milk maid’s grip: irregular contraction &
relaxations on squeezing examiner hand
Wormian movements of tongue upon protrusion
(Darting tongue).
Examination of handwriting to evaluate fine motor
movements
Outcome
Self-limited ; usually resolve within 4-8 weeks
Acute phase reactant are usually normal in isolated chorea
4. Erythema Marginatum (< 5%)

Site
The trunk
Proximal parts of the limbs
Criteria
Large erythematous macules.
With pale centers and serpiginous borders( map like
appearance)
Evanescent.(may come and go for several months)
Not pruritic
5. Subcutaneous Nodules (< 1%)

Appear several weeks after the attack
Site
Over the extensor surfaces of tendons near
bony prominences.
Criteria
Size is about 1 cm.
Firm, freely mobile,and painless.
Usually associated with severe carditis.
N.B: Both sub cutaneous nodules and erythema marginatum are rare in Egypt

Page | 44
Minor criteria of Rheumatic Fever
A. Clinical
1. Fever: of > 38° C (>38.5° C in Low-Risk populations)
2. Arthralgia
Moderate/High-Risk populations only include monoarthralgia
(polyarthralgia for Low-Risk populations)
Can’t be used as minor manifestation in presence of arthritis
B. Investigations
1. ECG: Prolonged P-R interval
Can’t be used as minor manifestation in presence carditis
2. Elevated acute phase reactants
- n ESR; >30 mm/hr (>60 mm/hr in Low-Risk populations).
- n C reactive protein
Evidence of recent Group A Streptococcal (GAS) infection
Positive throat culture Or

Elevated or increasing streptococcal antibody titers : ASO , Anti
Deoxyribonuclase (DNase) E , Anti hyaluronidase
American heart association’s revised Jones criteria (2015)

For diagnosis of initial attack of ARF
2 major manifestations, Or
1 major and 2 minor manifestations
Plus
Evidence of recent GAS infection
For diagnosis of recurrent attacks of ARF
2 major, Or
1 major and 2 minor, Or
3 minor manifestations (only in the Moderate/High-Risk
population)
Plus
Evidence of recent GAS infection
Carditis Redefinition (see before)
Arthritis Redefinition (see before)
Minor criteria Redefinition (see before)

Page | 45
Notes on Jones criteria

There are 3 circumstances in which the diagnosis of acute rheumatic fever can be
made without strict adherence to the Jones criteria:
When chorea occurs as the only major manifestation of acute rheumatic
fever
When indolent carditis is the only manifestation
Patients with recurrences of acute rheumatic fever in particularly high-risk
populations.
Prognosis and complications
1. Arthritis sub side within days to weeks even without treatment.
2. Chorea subsides within few months without residuals.
3. Only carditis can cause permanent damage especially in recurrences which :
* Suggested by: - Appearance of new murmurs.
- Change in character of already existing murmur
* Result in organic valve lesion e.g. MS,MR, AS, and/or combined valve lesion.
* Carditis and chronic valve lesions may be complicated by:
- Heart failure - Arrhythmias
- Infective endocarditis - Pulmonary hypertension
- Embolic manifestations
Differential diagnosis
1. Other causes of arthritis
R Post streptococcal arthritis
May follow infection with either group A or group G streptococcus
Typically oligoarticular, affecting lower extremity joints, and mild
symptoms can persists for months
Some clinicians consider it to be an incomplete form of acute
rheumatic fever
R Transient synovitis (toxic synovitis)
Post-infectious arthritis, typically affects the hip, often after an upper
respiratory tract infection
Acute onset of severe pain in the hip, with referred pain to the thigh or
knee, lasting approximately 1 wk
R Rheumatoid arthritis:
Chronic deforming arthritis; last 6 weeks.
Non migratory
Some involve small peripheral joints.
Absent dramatic response to salicylates within 48 hours.
Associations e.g. Spiking fevers, lymphadenopathy, and splenomegaly

Page | 46
R Reactive arthritis related to gastrointestinal infections (e.g., Shigella,

Salmonella, Yersinia)
R Septic arthritis (usually monoarthritis )
R Serum sickness
R Hematologic e.g. Sickle cell disease, Acute leukemia , hemophelia.
R Immunologic e.g. Systemic lupus erythematosis& anaphylacteod purpura
2. Other causes of carditis e.g.
Vial carditis
Infective endocarditis
Drug induced.
3. Other causes of chorea e.g
Wilson disease
Cerebral palsy
Treatment of Acute Rheumatic Fever
A. Treatment of Acute Attack
1. Eradicate group A Streptoccoci from the upper respiratory tract
Oral penicillin or erythromycin for 10 days or a single intramuscular
injection of benzathine penicillin
Long-term antibiotic prophylaxis after this initial course of antibiotic therapy
2. Typical migratory Arthritis
1. Bed rest for 2 weeks
2. Anti-inflammatory drug: Salicylates
50-70 mg/kg 50 mg/kg
- Dose: 50-70 mg/kg/day (max = 6 gram /day) For 3-5 days

- Then 50 mg/kg/d for 3 weeks.
- Then gradual withdrawal monitored by decline in ESR & CRP
- Side effects: Gastritis, GI bleeding(R/Gastriprotection),Reye syndrome
3. Daily examination is vital to pick carditis that can present within 2 weeks of
the onset
3. Carditis
1. Bed rest
- For cases with severe carditis and heart failure
- Rest for 3 months and gradual ambulation
for a similar period

Page | 47
2. Anti-inflammatory drugs
a. Corticosteroids (Prednisone)
* Indications:
- Moderate to severe carditis(with cardiomegaly)
- Heart failure.
* Dose
2 mg/kg
1 mg/kg Salicylates 50 mg/kg
2 mg/kg/d for 2-3 weeks

Followed by half the dose for 2-3 wk
And then tapering of the dose by 5 mg/24 hr every 2-3 days
At the beginning of tapering; salicylates is started at dose of 50
mg/kg/d and continued for 6 weeks to avoid rebound phenomenon.
b. Salicylates can be used in mild carditis without cardiomegaly nor heart

failure
3. Heart failure with respiratory distress
a. Oxygen inhalation
b. Restriction of salt and fluid intake.
c. Steroids
d. Other anti-failure drugs:
- Diuretic: Furosemide 1mg/kg every 6-12 hours
- VasoDilators: e.g. captopril
- Digoxin: used cautiously; begin with half the usual recommended dose
(Nelson Textbook of Pediatrics, 2016)
R Anti-inflammatory agents (e.g., salicylates, corticosteroids) should be withheld if arthralgia

or atypical arthritis is the only clinical manifestation of presumed acute rheumatic fever.
R Premature treatment with one of these agents may interfere with the development of the
characteristic migratory polyarthritis and thus obscure the diagnosis of acute rheumatic
fever.
R Acetaminophen can be used to control pain and fever while the patient is being observed for
more definite signs of acute rheumatic fever or for evidence of another disease
(Nelson Textbook of Pediatrics)

Page | 48
4. Treatment of Rheumatic Chorea

R Avoid emotional stress.
R Control abnormal movements:
- Phenobarbitone 16-32 mg / 8 hours oral Or
- Haloperidole (Safinase tablet) 0.01-0.03 mg/kg.
R Long acting penicillin prophylaxis.
5. Treatment of complications
- Treatment of heart failure; see before.
- Treatment of infective endocarditis
- Treatment of valve lesions
B. Prophylactic
1. Primary prevention: prevent 1st attack by:
- Hygienic housing.
- Proper treatment of Strept. infection: penicillin or erythromycin for 10 days.
2. Secondary prevention : Prevent recurrence of Rheumatic fever by:
R Long acting penicillin (Benzathine penicillin)
R Dose : 600.000 units for those < 27 kg and 1.2 million unit for those > 27 kg
R Route: Single injection, I.M every 3-4 weeks.
R Alternatives: Oral penicillin V or Macrolide (Erythromycin)
R Duration
Rheumatic fever category Duration
Without carditis 5 yr or until 21 yr of age, whichever is
longer
With carditis but without 10 yr or until 21 yr of age, whichever
residuals is longer
With carditis and residual 10 yr or until 40 yr of age, whichever
heart disease is longer
Sometimes lifelong prophylaxis
(Nelson Textbook of Pediatrics, 2016)
3. Infective Endocarditis (IE) prophylaxis

American heart association (AHA) no longer recommends routine IE
prophylaxis for rheumatic heart diseases
Prophylaxis is still recommended only for those with prosthetic valves or
prosthetic material used in valve repair (use antibiotic other than penicillin)

Page | 49
Definition
Infection of the valvular & mural endocardium
Infection can be bacterial, viral, or fungal
Pathogenesis
Two factors are essential
1. Presence of cardiac structural abnormality with significant pressure gradient
2. Bacteremia; even transient
Commonest causative organisms
1. Streptococcus viridans (50%):
Follows dental surgery ,dental caries, tonsillectomy, dental extraction
2. Staphylococcus aureus and epidermidis
Mainly postoperative
Risk is high with prosthetic valve and central venous catheter
3. Group D enterococci
More often after lower bowel or genitourinary procedures
4. HACEK group : Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and
Kingella species
4. Pseudomonas aeruginosa or Serratia marcescens
Seen more frequent in intravenous drug users
5. Fungal: Seen more frequent in immunodeficient & post open heart surgery.
Pathology
Implantation of the organism in the
diseased endocardium o Local
inflammation & formation of friable
vegetations composed of platelets, fibrin,
inflammatory cells, and organisms
Clinical picture
A. History: Suggestive of a risk factor or bacteremia
B. General manifestations
1. Fever (pyrexia)
2. Poor appetite o weight loss & malaise.
3. Palpable spleen (tender splenomegaly)
4. Pale clubbing
5. Pallor
6. Purpura

Page | 50
7. Rare manifestations due to immune complexes induced vasculitis:

Osler nodules Janeway macules Splinter hemorrhage
Transient tender nodules Irregular, painless Linear hemorrhagic
Pea-sized macules streaks
Intradermal
- in the pads of the In palms and soles Beneath the nails
fingers and toes
B. Cardiac manifestations
Appearance of new murmurs
Change in the character of previous murmurs
Sea gull murmur (musical) o due to rupture of valve leaflets.
Heart failure or arrhythmias.
C. Embolic manifestations
1. Neurologic
- Embolic stroke (seizures, hemiparesis)
- Cerebral abscess
- Mycotic aneurysm o intracranial hemorrhage
2. Pulmonary embolism 3. Retinal hemorrhages;

(Roth spots = oval with pale
centers), blindness
4. Renal infarction o 5. Skin infarcts and

hematuria & renal failure gangrene

Page | 51
Investigations
A. For diagnosis
1. Blood culture
3-5 blood samples before the start of antibiotics (contact the lab staff !!!)
The causative agent is recovered from the 1st 2 blood cultures in 90% of cases
2. Echocardiography: transthoracic and transesophageal
Value
Detects vegetations (early & minute vegetation < 3 mm3 may be missed)
May predict embolization (fungating vegetation > 1 cm3).
Detects underlying cardiac lesions
Detects complication e.g. valve dysfunction or leak , myocardial abscess
3. Culture of other specimens may include scrapings from skin lesions, urine,
synovial fluid, abscesses, and, CSF in case of meningitis
4. With unusual microorganisms
PCR of surgical material e.g. resected valve tissues
Specific serology
B. For monitoring/effect
1. Acute phase reactant (ESR, CRP, Procalcitonin and Leucocytosis)
2. Complete blood count: for anemia of chronic illness
3. Renal function tests, urinalysis
Prevention
A. Oral and dental care;the important
B. Antibiotic prophylaxis; Required for cases with:
1. Prosthetic cardiac valve 3. Congenital heart disease

or prosthetic material used (except ASD)
for cardiac valve repair 4. Repaired Congenital heart disease
with prosthetic material or device
5. Palliative shunts and conduits
2. Previous infective endocarditis 6. Permanently damaged valves

due to Rheumatic heart disease

Page | 52
Procedures requiring prophylaxis ?

R Dental /oral
R Invasive respiratory tract procedures
R Cardiac surgery/catheterization
x Prophylaxis for gastrointestinal or genitourinary procedures is no

longer recommended in the majority of cases
x Direct consultation with the child’s cardiologist is still the best method
for determining a specific patient’s ongoing need for prophylaxis
Prophylactic antibiotics
R Oral amoxicillin (50 mg/kg) or Ampicillin Or
R Ceftriaxone (50 mg/kg) IM or IV Or
R If penicillin allergic: Azithromycin or clindamycin
3. Vigorous treatment of sepsis and local infections
Treatment
Medical
1- Hospitalization, Bed rest and treat heart failure
2- Antibiotic therapy
Start immediate parenteral antibiotic combinations while waiting for
culture results.
For 4-6 weeks ( modify in view of clinical and laboratory response)
Best empirical therapy in patients without a prosthetic valve is
vancomycin plus gentamicin
Other antibiotics include crystalline penicillin G, ceftriaxone, nafcillin
or oxacillin.
Amphotricin B and 5 florocytosine for fungal endocarditis.
Surgical
x Removal of vegetation with or without valve replacement
x Indications
Treatment failure e.g. increasing size of vegetations while under
therapy
Complications: Severe valve involvement with intractable heart
failure, myocardial abscess, recurrent emboli
(American Heart Association 2007, Nelson 2016)
Prognosis: Despite the use of antibiotic agents, mortality is at 20-25%. Serious
morbidity occurs in 50-60%

Page | 53
Heart failure
Definition
Clinical syndrome in which the heart is unable to pump enough blood to
meet body needs.
Causes
Congenital heart diseases are the commonest Rheumatic heart diseases (in
causes of heart failure in infancy school age)
Myocarditis Acute hypertension
- Viral e.g. Coxachie A, B & Echo viruses Severe anemia
- Toxic e.g. drugs, diphtheria .
Dilated cardiomyopathy.
Dysrhythmia Acute cor pulmonale
Supraventricular tachycardia Broncho pulmonary dysplasia
Complete heart block
Nutritional e.g. Beri Beri, Kwashiorker, Keshan disease(selenium deficiency)
Clinical features
A. Symptoms
Infants
- Poor feeding; takes less volume per feeding, becomes
dyspneic while sucking, and may perspire profusely
- Poor weight gain.
Older child
- Dyspnea on exertion.
- Effort intolerance.
- Ankle edema.

Page | 54
B. Signs
Compensatory response to heart failure
1- Tachycardia, gallop rhythm & weak pulse.
2- Cardiomegaly is almost always present.
3- Cold, sweaty skin (increased sympathetic derive)
Pulmonary congestion
1- Tachypnea
2- Exertional dyspnea
- Infant o poor feeding.
- Child o dyspnea & orthopnea
3- Chest wheezes & fine crepitation.
Systemic congestion
1- Enlarged tender liver (may be absent in early left sided failure).
2- Congested neck veins; hard to detect in infants due to short neck.
3- Edema o generalized start in ankles (sacral in bed ridden)
4- Edema in infants usually involve eye lids and the sacrum
Investigations (Heart failure is a clinical diagnosis)

1. Chest X-ray
R Cardiomegaly
R Fluffy perihilar pulmonary markings
2. Echocardiography
R Confirm ventricular dysfunction
Using fractional shortening (difference
between end-systolic and end-diastolic
diameter divided by end-diastolic diameter)
Normal value is between 28% and 42%
R Doppler can estimate cardiac output
R May detect the cause of failure.

Page | 55
3. Magnetic resonance angiography (MRA)

Quantifies left and right ventricular function, volume and mass.
Quantifies the regurgitant fraction in valvar regurgitation
4. ECG: - Detect arrhythmias.
Treatment
1. Hospitalization
R Bed rest as needed in a semi-upright position(infant chair for infants)
R O2 inhalation ± positive pressure ventilation can significantly reduce total
body oxygen consumption
R Low salt diet o avoid further salt and water retention.
R Increasing daily calories (nasogastric feedings may be helpful)
R Sedation
2. Treat the cause
3. Improve the cardiac performance via:
Decrease the after load
(decrease peripheral vascular
resistance) by Vasodilators
Decrease the pre Increase myocardial

load by contractility by
Diuretics Digoxin/Inotropes
a. Diuretics
Acute heart failure
x Furosemide
I.V. ( 0.5-2 mg/kg/dose) or oral (1-4 mg/kg/day)
Precautions : monitor serum electrolytes and acid
base(Hypokalemia and alkalosis o may increase digitalis toxicity)
x Nesiritide (B-type natriuretic peptide) IV infusion
Chronic heart failure
x Spironolactone (potassium sparing diuretic)
x Thiazide duiretics
b. Vasodilators
Used if blood pressure allows and in absence of obstructive lesions
Actions
After load reducers
Cardiac remodeling

Page | 56
Commonly used drugs

Angiotensin converting enzyme (ACE) inhibitors e.g. Captopril,
Enalapril
Angiotensin receptor blockers [ARBs]
Indicated mainly in:
Dilated cardiomyopathy/myocarditis
CHD with large left to right shunt.
Severe MR and AR
Hypertensive heart failure
c. Digoxin
Digitalization
R Total digitalizing dose (TDD)
Oral TDD (microg/kg) I.V. TDD
Premature 20
Newborn 30 75% of oral T.DD.
Infants < 2 y 40-50
Child > 2 y 30-40
½ the TDD is given immediate
¼ TDD after 12 hours
¼ TDD after another 12 hours
R Precautions
Obtain ECG before each of the 3 digitalizing doses
Measure baseline serum electrolyte before and after digitalization
R Maintenance dose
Oral:5-10 μg/kg/day, divided q12h
IV dose is 75% of oral dose
Trough serum level: 1.5-3.0 ng/mL <6 mo old; 1-2 ng/mL >6 mo old
Absolute contraindications to digitalis
- Cardiac outlet obstruction e.g. Hypertrophic cardiomyopathy.
- Fallot’s tetralogy
- Heart block.

Page | 57
Other inotropes
Used for short term in ICU setting ;given by intravenous infusion
Dobutamine ± Dopamine
Milrinone( Phosphodiesterase inhibitor)
Digitalis toxicity
1. Causes
- Accidental over dose.
- Renal impairment.
- Increased myocardial sensitivity e.g.: hypokalemia & active myocarditis
- Drug interactions.
2. Signs
- Anorexia, vomiting
- Drowsiness & visual disturbance in older child.
- Bradycardia
- Worsening of heart failure.
- Arrhythmias (supraventricular arrythmia & heart block).
3. Treatment
R Continuous ECG monitoring.
R Stop digitalis
R Correct hypokalemia
R Correct arrhythmias by
a- Atropine 0.01 mg/kg/6 hours for heart block.
b- lidocaine for ventricular arrhythmia
R Increase excretion of digoxin by Digoxin immune Fab (Digibind), slow
I.V.

Page | 58
Systemic Hypertension
Definition
¾ Average systolic blood pressure (SBP) and/or diastolic blood pressure (DBP)
WKDWLVWKSHUFHQWLOHIRUDJHVH[DQGKHLJKWRQRFFDVLRQV
¾ 3UHK\SHUWHQVLRQZDVGHILQHGDVDYHUDJH6%3RU'%3WKDWDUHWKSHUFHQWLOH
but <95th percentile
¾ In adolescents beginning at age 12 yr, prehypertension is defined as BP between
120/80 mm Hg and the 95th percentile
Causes
1. Essential (primary) hypertension
Rare in children; common in adults.
Associations o obesity, hereditary, increased sensitivity to salt intake.
2. Secondary
Etiology Acute Chronic
Renal - Acute glomerulonephritis. Renal tumors, hypoplasia, dysplasia.
- Acute renal failure. Chronic pyelonephritis
- Hemolytic uremic Hydronephrosis/reflux nephropathy.
syndrome. Renovascular:
R Renal artery stenosis, thrombosis,
R Polyarteritis.
R Renal vein thrombosis.
Endocrine Cushing syndrome
Hyperaldosteronism
Congenital adrenal hyperplasia.
Hyperparathyroidism(hypercalcemia)
Tumors Neuroblastoma
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Pheochromocytoma
Cardiac Coarctation of aorta
Neurologic Acute n intra cranial

tension.
Guillian Barre syndrome
Poliomyelitis.
Drugs - Sympathomimitics. - Steroids - NSAIDs

Page | 59
Possible mechanisms in 2ry hypertension

Stimulation of Renin-Angiotensin-Aldosterone system e.g. renal hypertension.
Salt & water retention e.g. Cushing & hyperaldosteronism.
Stimulation of vasomotor center e.g. neurologic hypertension.
Vasoconstriction due to:
n Release of catecholamines e.g. pheochromocytoma
Sympathomimitc drugs.
Presentation
1- Usually asymptomatic.
2- May be o headache, irritability, blurr of vision (in severe cases)
3- Complications
* Hypertensive heart failure.
* Acute pulmonary oedema.
* Hypertensive encephalopathy :
Severe bursting headache, vomiting,
Irritability, convulsions and coma.
Fundus examination
R Vasospasm
R Papilloedema
R Retinal hemorrhage.
Investigations
24 hour Ambulatory Blood Pressure Monitoring (ABPM).
Calculate mean daytime BP, and sleep BP over 24 hr.
ABPM is useful in the evaluation for:
White coat hypertension
Risk of hypertensive target organ damage
Response to pharmacologic therapy (confirms physiologic nocturnal
dipping of blood pressure essential for kidney vitality)
Workup for 2ry causes
1. Renal
Urine analysis, urine culture, renal function tests.
Abdominal ultrasound.
Renal Doppler.
x If blood pressure is QRWFRQWUROOHGRQGUXJV
Pre and post captopril renal scintigraphy and or
CT or MRI angiography
x If strong suspicion of renovascular hypertension
Digital Subtraction Angiography
Selective renal vein rennin level

Page | 60
2. Cardiac
Chest X-ray
Echocardiography (For a cause or effect of hypertension).
3. Endocrinal
Electrolytes (potassium & sodium).
Night time blood or salivary cortisole level on in Cushing.
4.Tumors
24hr urine vallynile mandilic acid (VMA); (metabolite of catecholamines)
on in pheochromocytoma & Neuroblastoma.
Abdominal ultrasound, CT, MRI.
Treatment
R Children with BP between the 95th and 99th percentile plus 5 mm Hg are
categorized as stage 1 hypertension
R children with BP above the 99th percentile plus 5 mm Hg have stage 2
hypertension.
R Stage 1 hypertension, if asymptomatic and without target organ damage, allows
time for evaluation before starting treatment
R Stage 2 hypertension calls for more prompt evaluation and pharmacologic
therapy
Goals
Reduce BP below the 95th percentile
In the presence of chronic kidney disease, diabetes, or target organ damage, the
goal should be to reduce BP to less than the 90th percentile
If blood pressure between 90 -95th percentile continue monitoring
A. Chronic hypertension
I. Primary hypertension
1. Non pharmacologic
- Weight reduction may result in a 5-10 mmHg reduction in systolic pressure
- Low salt, potassium rich diet
- Dynamic aerobic exercises
- Physical fitness
2. Drug therapy
Indications
- Family history of early complications of hypertension
- Target organ damage (ocular, cardiac, renal, neurologic)
- Symptomatic hypertension

Page | 61
Stepped care approach

Step 1: A small dose of single antihypertensive drug either diuretic or an
adrenergic inhibitor
Step 2: If the first drug ineffective a second drug is added to or substitute
the initial drug starting with small dose then proceed to a full dose.
Step 3: If blood pressure is still high a third drug; usually a vasodilator, is
added
Drugs
* Diuretics e.g. hydrochlorothiazide, chlorothiazide, spironolactone
* Adrenergic inhibitor e.g. atenolol, prazocin
* Vasodilator e.g.
Hydralazine
ACE inhibitors e.g. captopril , enalapril
Calcium channel blockers e.g. nifedipine, amelodipine
II. Secondary hypertension
Treat the cause whenever possible
Drug therapy as in essential hypertension
B. Acute hypertension
x The blood pressure should be reduced by 10% in the 1st hour, and 15% more
in the next 3-12 hr, but not to normal during the acute phase of treatment
x Hypertensive urgencies, usually accompanied by few serious symptoms such
as severe headache or vomiting, can be treated either orally or intravenously.
Action plan
1. Ensure safe airway, breathing and circulation (ABC)
2. Slow reduction of blood pressure is mandatory.
3. Drugs useful in acute hypertension:
With severe symptoms
Hydralazine 4 hourly IM,IV
Labetalol IV infusion
Esmolol IV infusion
Nicardipine IV infusion
Sodium nitroprusside IV infusion
With less severe symptoms PO
Clonidine, hydralazine, or isradipine.
Minoxidil is the most potent oral vasodilator; long-acting
4.Treat the cause (in 2ry hypertension).
5.After adequate control of acute hypertension shift to oral antihypertensives

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Page | 62

Introduction to Pediatric Hematology
Intrauterine hematopoiesis passes into 3 stages:
Yolk sac hematopoiesis Visceral hematopeiosis Medullary hematopeiosis
st th th
In the 1 8 weeks 8 week o 6 month 6th month o onwards
In the yolk sac In the liver, spleen, Settles in the bone marrow
lymph nodes & thymus
Exposure to hematologic stress (e.g. chronic hemolysis) o ++ bone marrow then
++ extramedullary hematopoiesis in the spleen and the liver.
Bone marrow contain pleuripotent stem cells which give colony forming unit (CFU):
R ErythroidoErythroblastsoNormoblastsoReticulocytesoRBCs
R MyeloidoMyeloblastoPromyelocyteoMyelocyteoMetamyelocyteo mature WBCs
R Megakaryocytic oMegakaryoblastoMegakaryocyte oPlatelets
xNormal erythropoiesis requires
Regulatory hormones Essential nutritional
Erythropoietin elements
Androgen - Proteins
Thyroxin - Iron
ACTH - Folic acid
Cortisol - Vitamin B12
x Normal stem cells in bone - Copper
Growth hormone marrow
Hemoglobin (Hb) composition
Hb molecule is composed of Heme groups (ferrous iron containing)
attached to 4 polypeptide chains which define the type of Hb.
Types of normal hemoglobins
1. Emberyonic hemoglobin :
Gower 1, 2 and Portland
Disappear by the 3rd month
2. Foetal hemoglobin
Hb F (D2, J2)
Has high affinity to O2
3. Adult hemoglobin: Hb A (D2, E2),Hb A2 (D2, '2)
Switch mechanism in hemoglobin synthesis
Emberyonic life 6th month At Birth 6-12 month postnatal
Emberyoic Dominant -- -- --
Hb F -- 90 % 70 % <1%
Hb A -- 10 % 30 % 97 %
Hb A2 -- -- Trace 2%
rd th
* At the 3 – 6 month o normal switch from J to E chain production occurs

Page | 63

Blood indices
Hemoglobin content:
- In 1st 2 weekso 16-20 gm/dl (intrauterine hypoxia onerythropoietin).
- In infancy o 10-14 gm/dl
- Adult male o 13.5- 17.5 gam/dl
- Adult female o 11.5 – 15.5 gm/dl
RBCs count:
- In newborn o 6 million / mm3.
- Adult male o 4.5- 6 million / mm3
- Adult female o 4 - 5.5 million / mm3
Hematocrite value(Ht. value) ; packed red cell volume
* Percent of RBCs volume in 100 ml blood | 40-50%
* Increased in
Polycythemia
Hemoconcentration(dehydration)
* Reduced in
Anemia
Hemodilution
Mean corpuscular volume (MCV)
- Normal: 72 – 79 femto liter.
- If < 70 o RBCs are small (Microcytes).
- If > 85 o RBCs are big (Macrocytes)
Mean corpuscular hemoglobin (MCH)
- Normal: 27- 34 pg.
- If < 27 pg o RBCs are hypochromic.
Mean corpuscular hemoglobin concentration (MCHC)
- Concentration of Hb. in an erythrocyte
- Normal: 33%
- If < 30 % o RBCs are hypochromic
Reticulocytic count (RC)
* In neonatal period < 5 %
* Later on 0.5 – 1.5 %
* Reticulocytosis occur in:
- Hemolytic anemia.
- Hemorrhage
- Response to hematinic e.g. (iron, folic acid)
- Recovery of bone marrow from suppression.
* Reticulocytopenia occur in bone marrow failure
White blood cells count
In neonatal period =15.000 – 20.000 / mm3
Later on = 4.000 – 11.000 / mm3
Platelet count 150.000 – 450.000 / mm3

Page | 64
Anemia
Definition
Reduction of hemoglobin and/or RBCs count
Below the average value for age and sex
Interfering with oxygen carrying capacity of blood
General features of anemia

Symptoms (all are non-specific) Signs (all are non-specific)
Fatigue, headaches and faintness are Pallor
all very common Tachycardia (palpitation)
Palpitations
Breathlessness Hemic murmurs (functional, systolic).
Angina Heart Failure in severe anemia (with
Intermittent claudication hemoglobin < 4 gm/dl)
Classification of anemia
A. Morphologic Classification
Microcytic anemia Normocytic anemia Macrocytic anemia

MCV < 70 fl 72-79 fl >85 fl
B. Etiologic Classification
I. Decreased production
a. Decreased erythroid cells in bone marrow

(Bone marrow failure)
Pure red cell anemia.
Aplastic anemia
Marrow infiltration e.g. Leukemia
b. Decreased red cells production despite

normal RBCs precursors
* Anemia of chronic disease:
Chronic inflammation
Chronic infection
Chronic renal failure
c. Specific factor deficiency (Dyshemopiotic anemia) e.g. deficiency of

* Minerals: Iron, copper * Vitamins: B1, B6, Folic acid and B12. * Protein

Page | 65

II. Increased destruction (hemolytic Anemia)
A. Intra corpuscular causes
a. Membrane defects
- Hereditary spherocytosis
- Hereditary elliptocytosis.
- Paroxysmal nocturnal
hemoglobinuria
b. Hemoglobinopathy
- D thalassemia
- E thalassemia. c. Enzymatic defects
- Sickle cell disease - G6PD deficiency
- Pyruvate kinase
deficiency.
B. Extra corpuscular causes
Immunologic Non immunologic

(Coombs test Positive) (Coombs test Negative)
1. Iso immune hemolytic anemia 1.Microangiopathic Hemolytic Anemia(MAHA)
(passively acquired antibodies) - DIC
- Hemolytic disease of newborn - Hemolytic Uremic Syndrome (HUS).
- Incompatible blood transfusion - Renal Vein Thrombosis (RVT).
- Artificial & Calcified Cardiac Valves
- Disseminated Cancer
2. Autoimmune hemolytic anemia - Thrombotic Thrombocytopenic Purpura
(actively formed antibodies): 2. Septicemia (E.G. Clostridia Welchii)
- Idiopathic 3. Malaria Due To: - Direct Effect
- Secondary - Drug Induced
4. Drugs, Heavy Metals, Snake Venom
5. March Hemoglobinuria
6. Paroxysmal Nocturnal Hemoglobinuria
7. Hypersplenism
III. Hemorrhagic anemia

- Acute hemorrhage
- Chronic hemorrhage.

Page | 66
Bone Marrow
Failure
A.Trilineage failure
&ULWHULD - Failure of the 3 cell lines with pancytopenia
- No organomegaly nor lymphadenopathy.
&DXVHV
a. Congenital
1. Fanconi anemia
2. Familial aplastic anemia
3. Dyskeratosis congenital; Ectodermal dysplasia with:
R Skin pigmentation
R Mucous membrane leukoplakia
R Nail dystrophy
R Others : short stature ,cataract, mental retardation
b. Acquired
1. Idiopathic
2. Secondary
B. One cell line failure
5HGFHOOV (hypoplastic anemia;pure red cell anemia)
a. Congenital
- Diamond Blackfan anemia
- Congenital dyserythropoietic anemia
- Pearson's Syndrome
b. Acquired
* Idiopathic: transient erythroblastopenia of childhood
* Secondary: to Drugs, Infections, Parvo B19 , Malnutrition
:KLWHFHOOV
1. Schwashman Diamond syndrome: pancreatic insufficiency, metaphyseal
dysplasia
2. Kostmann disease (severe congenital neutropenia)
3. Reticular dysgenesis
3ODWHOHWV
1. Congenital amegakaryocytic thrombocytopenia
2. TAR syndrome (thrombocytopenia absent radii syndrome)
N.B : Dyserythropoiesis (ineffective erythropoiesis).

i. Primary (congenital dyserythropoietic anemia).
ii. Secondary dyserythropoiesis:
- Megaloblastic anemia (folic acid, or vit B12 deficiency).
- Thalassemia syndromes.
- Sideroblastic anemia.
- Paroxysmal nocturnal hemoglobinuria

Page | 67
Aplastic anemia
Definition
Marked decrease or absence of blood forming elements in the bone marrow (BM)
with peripheral pancytopenia (decreased RBCs, WBCs and platelets).
Etiology
1. Congenital aplastic anemia: e.g. Fanconi anemia
2. Acquired aplastic anemia.
Idiopathic (50%)
Secondary
- Irradiation
- Insecticides
- Infections e.g. Ebstein Barr virus, hepatitis viruses , HIV
- Drugs o Dose dependent bone marrow depression e.g. chlorambucil
o Idiosyncratic non dose dependent BM depression by:
- Antibiotics o Chloramphenicol , sulphonamides
- Anticonvulsants o Carbamazepine, phenytoin
- Antithyroid o Carbimazole, thiouracil
- Antimalarial o Chloroquin
- Antirheumatic o Indomethacin, phenylbutazone
- Diseases o SLE, Paroxysmal nocturnal hemoglobinuria (PNH)
Pathogenesis Of acquired aplastic anemia:
Theory: Altered bone marrow stem cells antigen proteins e.g. by drugs or
infection o Activated T lymphocytes o ĹTNF and Interferon Ȗ o accelerated
stem cells apoptosis o pancytopenia.
Aplastic anemia is unstable condition; may progress to myelodysplastic
syndrome and leukemia
Clinical picture
R Thrombocytopenia opurpura
R Anemia o pallor (+ ZHDNQHVVIDWLJXHHWF«« )
R Lecuopeniao frequent, persistent infections
R No organomegaly (no hepatosplenomegaly nor lymphadenopathy).

Page | 68

Fanconi anemia
Inheritance: Mainly autosomal recessive
Clinical features
Microcephaly / mental
Skeletal anomalies (60%) retardation (17 %)
Triangular facies
Abnormal thumb
(absent or hypoplastic)
Congenital anomalies
Absent radii
e.g.
Eye
Short stature with short
trunk Ears
Cardiac
Renal
Skin pigmentation (café Genital
au lait spots) mainly over
the trunk
Hematological
x High risk of malignancy e.g. acute myeloid
leukemia and solid cancers
x Pancytopenia :
- Typically starts with thrombocytopenia or
leukopenia
- Usually between 4th – 12th year (earlier or
later presentation do occur)
- Bone marrow is aplastic
Investigations
1. CBC
Pancytopenia (with macrocytic anemia)
Reticulocytopenia
2. BM
Hypo cellular BM
Replaced by fibro fatty tissue.
3. In Fanconi anemia :
Cytogenetic of blood lymphocytes shows
increased chromosomal breakages and exchanges
induced by mutagen (e.g. Mitomycin C)
Mutation analysis
4. Investigations for a cause e.g. viral serology

Page | 69

1- From other causes of pancytopenia
2- From other causes of purpura e.g. Idiopathic thrombocytopenic purpura.
Treatment
1. Supportive care; see leukemia
2. Specific treatment: Indicated in severe aplastic anemia
a. For Fanconi anemia
1. Androgen therapy (Oxymetholone) effective in 50 %
2. Hematopoietic stem cell transplantation (HSCT) from HLA matched
donor
b. For acquired aplastic anemia
1. Hematopoeitic stem cell transplantation from HLA matched donor
2. If HSCT was unavailable use (alone or in combination):
- Anti thymocyte globulin
- Cyclosporine
- Methyl prednisolone
- Granulocyte colony stimulating factor (G-CSF)
Causes of pancytopenia:
* Bone marrow failure e.g.
- Aplastic anemia
- Advanced megaloblastic anemia
- Myelophthisis: Bone marrow infiltration
* Hypersplenism (Pancytopenia with compensatory bone marrow hyperplasia)
* Fulminant sepsis
* Auto immune (Evans syndrome)

Page | 70

Congenital Pure red cell anemia
(Diamond Blackfan Anemia)

Definition
Familial disease due to decreased sensitivity of erythroid cells to erythropoietin o
hypoplasia of RBCs precursors.
Clinical picture
R Pallor: usually evident by the 2nd – 6th months.
R Associated anomalies
- Abnormal thumbs; (triphalangeal thumb)
- Congenital heart diseases.
- Short stature
R Hepatosplenomegaly, if present, is due to
chronic transfusion therapy.
R High risk of acute myeloid leukemia.
Investigations
1. CBC
- Macrocytic anemia &reticulocytopenia
- Normal platelets and WBCs.
- Increased erythrocyte adenosine deaminase activity (ADA)& hemoglobin F
2. BM
- Decreased erythroid cells.
- Normal myloid and megakaryocytic cells.
Treatment
1- Steroids: Give remission in 80%.
2- Chronic transfusion therapy with iron chelation for steroid resistant cases
3- Bone marrow transplantation.
Differential Diagnosis
Form acquired pure red cell anemia
* Idiopathic: Transient erythroblastopenia of childhood;
- Due to transient immunologic suppression of RBCs synthesis
- No anomalies
- Normocytic normochromic red cells
- Usually need no treatment (recover within 1-2 months).
* Secondary: to Drugs, Infections, Parvo B19, Malnutrition

Page | 71
Iron Deficiency Anemia (IDA)

Incidence: The most common cause of anemia in pediatrics.
Iron metabolism
- Daily requirements: 8-15 mg/day
- Most of dietary iron present in ferric state.
- Iron changes to ferrous by combined action of HCL & vitamin C.

- Only 5-10% of dietary iron is absorbed from the duodenum and proximal jejnum
- Factors enhancing absorption e.g. decreased hipcidin, vitamin C, Ĺerythropoiesis

- Factors impairing absorption e.g. increased hepcidin, hypochlorhydra, tannate
- Absorbed iron is bound to serum transferrin and stored as ferritin to be used in

a. In bone marrow o RBCs
b. In cell enzymes e.g. Catalase, peroxidase, mono amine oxidase (MAO).
Iron homeostasis regulation
Hepcidin as the main regulator of systemic iron homeostasis

Hepcidin synthesis is induced by iron loading and inflammation and suppressed
by erythropoiesis.
Increased hepcidin levels limit further enteral iron absorption and release of
iron from the liver and the reticuloendothelial system to normalize plasma iron
levels.
With increased inflammation, elevated hepcidin levels cause the same sequence
of events, leading to reticuloendothelial blockade and the anemia of
inflammation.

Page | 72
Causes
1. Decreased intake In infants 6-24 months due to:
a. Delayed weaning (Prolonged b. Unfortified animal (Cow) milk feeder

breast-feeding without Due to:
supplementation) due to: Low iron content
Depletion of the baby’s iron Low lactoferrin content
store by the 6th month Presence of heat labile protein
Iron in breast milk is no more which induces occult blood loss
enough beyond 6th month
2. Decreased iron absorption

- Excess tea, phytate & antiacids
- Achlorhydra e.g. atrophic gastritis
- Malabsorption syndrome
3. Decreased iron stores
- Iron deficient pregnant
- Perinatal blood loss.
- Preterm.
4. Increased loss
a. Occult blood loss due to
- Ankylostoma - Peptic ulcer, polyps, GERD
- Cow milk protein allergy - Meckle’s diverticulum
- Drug induced gastritis. - Esophageal varices
b. Overt blood loss e.g

Epistaxis, hematuria, hemodialysis

Page | 73
5. Increased requirements due to:

Accelerated rate of growth in preterm,
infants, adolescence.
Congenital cyanotic heart diseases (due to
polycythemia)
Clinical picture
1. Mild anemia is asymptomatic.
2. Manifestations of anemia (anorexia, pallor,…) vary with severity of iron
deficiency.
3. Systemic manifestations:
x Decreased Alertness, learning &
concentration span (due to p iron
containing cellular enzymes).
x Atrophic glossitis : tongue

is pale ,glazed (smooth)
x Angular stomatitis
x Palpitation (Tachy cardia)
on exertion
x Cardiomegaly in severe
deficiency
x Nails Brittle , longitudinal

ridges, flattening and
spooning (koilonychia)
x Palpable spleen in about
10 % of cases
x Pica (Geophagia) desire to ingest unusual substances e.g. dirts
, mud ,chalk (increases the risk of concomitant lead poisoning)
4. Clinical signs of an underlying cause e.g. Ankylostoma anemia
Iron deficiency anemia plus
- Parotid enlargement (endemic parotitis)
- Recurrent abdominal Pain
- Bouts of diarrhea and constipation
- B complex vitamins deficiency: pellagra , nutritional edema
- Eosinophelia in the CBC and ova in stool analysis

Page | 74
Investigations
A. For diagnosis
1. CBC
Anemia: p Hb%, p RBCs count
Hypochromia: - MCH < 27 Pg
- MCHC < 30%
Microcytosis MCV < 70 fl
* Blood film shows:
Abnormally large central pallor (hypochromic cells)
Target cells
Wide red cell distribution width (RDW) and anisocytosis
* Normal white blood cells
* Thrombocytosis is often present
2. Iron indices
Index Iron deficiency normal range
R Serum Iron. < 30 Pg / dl 60 - 140 Pg / dl
R Transferrin saturation. < 16 % 30%
R Total iron binding capacity (TIBC) Increased 250-400Pg / dl
R Soluble serum transferrin receptors Increased Variable cutoff
Serum ferritin (index of iron stores) < 15 ng / ml 15-300 ng/ml
Reticulocyte hemoglobin content * < 27.5 pg
Marrow iron stores Absent
Hepcidin** Usually 10 ng/mL
*
A sensitive indicator that falls within days of onset of iron-deficient erythropoiesis and is
unaffected by inflammation
**
Extremely elevated in anemia of inflammation and suppressed in iron deficiency anemia
B. For the cause
- Stool analysis for parasites, ova and occult blood tests
- GIT barium study, endoscopy,and tests for achlorhydra
- Workup for malabsorption
- Workup for hemorrhagic diseases
Treatment
1. Treat the cause
2. Diet
Excessive intake of milk, particularly bovine milk, should be limited
infants who are breast and cow milk feeders require prophylactic oral iron
given at 4th – 6th months (2mg/kg/d)
in weaned; encourage intake of vitamin C, meat, fish

Page | 75

3. Iron preparation
Oral Iron
R Dose:3- 6 mg/kg/d. elemental iron
R In-between meals
R Continued for 8 wk after blood values normalize to re-establish iron stores
R Side effects: GIT upset, constipation and dark stool.
R Preparations:
Ferrous sulphate (The best; contain 20 % elemental iron)
Ferrous gluconate
Ferrous lactate
Parentral Iron
R Preparation
Iron Dextran (Imferon) or Iron sucrose (Venofer) IV
Iron sorbitol (Jectofer) deep IM
R Indications
Intolerance to oral iron
GIT disorders aggravated by oral iron e.g. IBD
Malabsorption
Rapid loss of iron
R Side effects
:LWK,0ĺVWDLQLQJDEVFHVV
:LWK,9ĺDQDSK\OD[LV VWDUWZLWK an observed test dose)
4. Packed red cell transfusion: is considered in
Severe anemia (Hb < 7- 8 gm/dl).
Anemic heart failure.
Infection interfering with iron therapy.
Response to iron therapy
Time after iron
Response
administration
Replaced cellular enzymes o decreased irritability
st
By the 1 day and
improved appetite.
nd
By the 2 day Erythroid hyperplasia in bone marrow.
rd
By the 3 day Reticulocytosis peaking at 5-7days
st
By the 1 month Increase hemoglobin at rate of 0.25 – 0.5 gm/dl/day
rd th
By the 3 - 6 months Repletion of stores.
Mentzer index (MI) = Packed cell volume / RBC count in millions
* Help differentiate microcytic anemia of iron deficiency from E thalassemia trait
* MI In iron deficiency anemia >13 * MI In E thalassemia trait <13

Page | 76
Differential Diagnosis of microcytic anemia that fails to respond to oral iron

1. Poor compliance / incorrect dose or medication
2. Malabsorption of administered iron
3. Ongoing blood loss
4. Concurrent infection or inflammatory disorder inhibiting the response to iron
5. Concurrent vitamin B12 or folate deficiency
6. Diagnosis other than iron deficiency
a) Hemoglobinopathies: Thalassemia , Sickle thalassemia , Hemoglobin C and
hemoglobin SC disease
b) Anemia of chronic disease
In any disease with chronic inflammation e.g. Chronic infections
Anemia is usually normocytic ; occasionally microcytic
Inflammatory mediators and raised Hepcidin are the main etiologies
c) Lead poisoning
History of exposure or iron deficiency with Pica
Blue staining of gums, abdominal pain
Lab: Basophilic stippling of RBCs ,high serum lead level, free erythrocyte
protoporphyrin
d) Siderblastic anemia (X-linked disorder)
Due to abnormal erythrocytic 5-aminolevulinic acid synthetase (ALAS), the
rate-limiting enzyme reaction in heme synthesis. An important cofactor for
ALAS is pyridoxal phosphate.
Treatment: Stem cell transplantation for transfusion dependent cases
IDA Anemia Of Thalassemia Sideroblastic
Chronic Disease traits Anemia
Serum Ferritin Decreased Increased Normal Increased
Serum iron Decreased Decreased Normal Increased
TIBC Increased Decreased Normal Normal
Transferrin Decreased Decreased Normal Increased
saturation
Bone Marrow Absent iron Increased iron Normal iron Increased iron
Ringed sideroblasts
Specific ĹĹ6ROXEOH Normal soluble Electrophoresis HSM, icterus
transferrin transferrin May respond to B6
receptors receptors
ĻĻ+HSFLGLQ ĹĹ+HSFLGLQ
High CRP
(Nelson textbook of pediatric)

Page | 77

Megaloblastic anemia
Definition: Anemia with megaloblasts in BM and macrocytes in peripheral blood.
Causes
i- Vitamin B12 (cobalamin) deficiency
ii- Folic Acid deficiency.
Pathogenesis
Folic acid & B12 are essential for DNA synthesis in stem cells of RBCs, platelets
and WBCs. So in folic acid or B12 deficiency
Nucleus can’t divide While RNA is normal
p RBCs production nn Cytoplasm.
n Megalobasts in BM
Macrocytes in blood Can’t leave BM.

(with nuclear remnants; Howell Jolly
bodies and Cabot rings)
Trapped prematurely in the spleen Intramedullary lysis
Extramedullary lysis
Metabolism
Vitamin B12 Folic acid
Sources
Animal origin only e.g. milk, meat. - Animal & plant (green leaves, fruits)
Requirements
5 – 20 Pg /day 20 – 50 Pg /day
Absorption
Gastric parietal cells release intrinsic Absorbed from the proximal intestine
factor (IF) which binds to B12 o (duodenum and jejunum)
B12/IF complex o absorbed from Requires vitamin C for absorption
the terminal ileum
Stores enough for 2-4 years Stores enough for 2-4 months

Page | 78

Causes of B12 and folic acid deficiency
Vitamin B12 Folic acid
Decreased * Infants breast fed to * Infants fed on: Goat’s milk
intake vegetarian mums
Decreased * Malabsorption syndrome * Malabsorption syndrome
absorption * Intrinsic factor defect * Vitamin C deficiency
- Pernicious anemia
- Gastrectomy
* B12 /IF consumption by
Diphyllobothrium latum or
bacterial overgrowth.
* Ileal disease Or resection
Impaired Defective transport: * Cytotoxic drugs o methotrexate
metabolism Transcobalamin II deficiency * Anticonvulsant o phenytoin
o valproate
Others . * Increase requirements: e.g.
- Prematures (pstores)
- Pregnancy
- Chronic Hemolytic anemia
* Reduced stores: liver cirrhosis
* Increased loss: hemodialysis
Clinical picture
A. Hematologic
* Anemia (Anorexia, pallor, tiredness , ……..) with slight jaundice.
* Advanced megaloblastic anemia o thrombocytopenic purpura and leucopenia
* Mild hepatosplenomegaly due to intramedullary hemolysis
B. GIT manifestations esp. in folate deficiency:
* Atrophic glossitis o Beefy red glazed tongue in 25 %
* Atrophic gastritis o Dyspepsia, vomiting, risk of cancer stomach
* Atrophy of intestinal mucosa o Abdominal pain and chronic diarrhea.
C. Neurologic manifestations: Sub acute Combined Degeneration (SCD)

Only with severe vitamin B12 deficiency (? irreversible)
* Degeneration of
- Posterior column o deep sensory loss, sensory ataxia
- Pyramidal tract o Progressive weakness, Paraplegia
- Peripheral Nerve o Symmetrical paraesthesiae in fingers & toes

Page | 79

Diagnosis
1. Is it megaloblastic anemia?
CBC
Macrocytic anemia Hyper segmented (hyper mature)

neutrophils (contain 4-5 lobes).
Low Hb% & Ht value

MCV > 100 fl
MCHC = normal
Thrombocytopenia, leucopenia and reticulocytopenia in advanced cases.
BM
Erythroid hyperplasia
Megaloblastic changes
2. What is the cause?

A. Vitamin B12 deficiency
i. Is there Vitamin B12 deficiency?
Low serum vitamin B12 (Diagnostic)
Therapeutic test: 1 Pg B12 o reticulocytosis at 6th day
ii. What is the cause of Vitamin B12 deficiency?
a. Schilling test: done if the etiology was unclear
Radioactive B12 is given orally followed by an I.M. injection of
non-radioactive B12 to saturate B12 binding proteins
Normally If this is abnormal
>10 % of oral B12 excreted in The test is repeated with the addition
urine of oral intrinsic factor capsules

Page | 80

Repeat test with oral radioactive B12 plus oral intrinsic factor
If the excretion is now normal If the excretion is still abnormal
Pernicious anemia or gastrectomy Terminal ileum lesion or bacterial

Overgrowth
Excretion is not corrected by Excretion is corrected by

antibiotics antibiotic course
Terminal ileum lesion Bacterial overgrowth
b. Gastric function tests: Histamine or pentagatrin test confirm achlorhydra

c. Serological tests: Anti-parietal and anti-IF antibodies
B. Folic acid deficiency
* Low serum folate; RBC level is better measure of tissue folate (Diagnostic)
* Therapeutic test: 0.2 mg Folate o look for reticulocytosis at 6th day
Treatment
A. B12 deficiency
a. Pernicious anemia
Hydroxocobalamin IM 1000 Pg to a total of 6 mg over the course of 3
weeks Then 1000 Pg every 3 months for the rest of the patient’s life.
Recent alternatives: high oral or sublingual dose 2 mg per day
b. Gastrectomy or ileal disease:
Monitor serum B12owhenever low o give prophylactic vitamin B12
c. Treat the underlying disease
B. Folic acid deficiency
a. Treat the underlying disease
b. Exclude subclinical B12 deficiency which ca be aggravated by folic acid
therapy
c. Folic acid 5 mg/day continued for 4 months to replace body stores.
d. Prophylaxis
Chronic hemolytic anemia 5 mg weekly
Premature<1500gm require 1 mg daily for 6 weeks
N.B:
Folic acid may produce a hematological response in vitamin B12 deficiency but
may aggravate the neuropathy. So Large doses of folic acid alone should not be
used to treat megaloblastic anemia unless the serum vitamin B12 level is known
to be normal

Page | 81
Hemolytic Anemia
Definition
Anemia resulting from increased RBCs destruction exceeding bone marrow
capacity for compensation (reduced RBCs survival).
Normal RBCs life span 120 days.
Acute Hemolytic Anemia

(Intra vascular hemolytic anemia)
Causes
A. Intra corpuscular causes: - Enzymatic defects e.g. G6PD deficiency
Immunologic Non immunologic

(Coombs positive) (Coombs negative)
Isoimmune Autoimmune 1. Microangiopathic hemolytic Anemia (MAHA)

Can be acute or chronic hemolytic anemia)
- Hemolytic disease - DIC
of newborn. - Hemolytic uremic syndrome (HUS).
- Mismatched blood - Renal vein thrombosis (RVT).
Transfusion. - Artificial & calcified cardiac valves
- Disseminated cancer
- Thrombotic thrombocytopenic purpura
2. Septicaemia (e.g. Clostridia Welchii)
3. Malaria due to: - Direct effect
- Drug induced
4. Drugs, heavy metals, snake venom
5. March hemoglobinuria
6. Paroxysmal nocturnal hemoglobinuria
General clinical manifestations

Acute pallor.
HyperBilirubinemia: - Indirect; lemon yellow color
- Dark colored urine (hemoglobinuria)
Pyrexia and rigors.
Loin Pain.
In Profound anemia: rapid decompensation with blurred vision, lassitude and
anemic heart failure even death

Page | 82
General workup
1. Anemia: Usually normocytic normochromic , low Hb% and Ht. value.
2. Decreased RBCs Survival indicated by:
- n Plasma hemoglobin
- n Metheamalbumin
- p Haptoglobin & haemopexin (hemoglobin carriers).
- n Serum LDH
- n Unconjugated bilirubin - Hemoglobinuria

- Heamosiderinuria
3. Increased erythropioesis indicated in the CBC by:
- Reticulocytosis: Reticulocytic count > 8%
- n Normoblasts (immature nucleated RBCs).
Specific investigations
1. Coombs test (Anti Globulin Test): Diagnose Immunologic hemolytic anemia.
Direct Coombs test detect antibody coated RBCs
Indirect Coombs test detect free antibodies in serum
2. Blood film for:

- Heinz bodies in G6PD deficiency.
- Microangiopathic hemolytic anemia: - Fragmented RBCs (schistocytes).
- Thrombocytopenia.
- Malaria.

Page | 83
Glucose - 6 - Phosphate Dehydrogenase Deficiency

(G6PD Deficiency)
Etiology
* Hemolytic anemia due to age labile Glucose - 6 -
Phosphate Dehydrogenase enzyme
* Sex linked recessive disorder which seen mainly in males
* Occasionally seen in females if in homozygous state or
heterozygous state with random inactivation of the other
normal X chromosome (Lyon hypothesis).
Pathogenesis
* G6PD enzyme is key enzyme of Hexose Mono Phosphate (HMP) shunt which
produce reduced glutathione.
* Reduced glutathione protects the red cells against oxidizing agents.
* In G6PD deficiency o p reduced glutathione o impaired elimination of oxidants

o oxidation of Hb o methemoglobin o precipitate inside RBCs o acute
hemolysis.
Oxidizing agents include
Food o Fava beans (favism)
contain vicine and convicine oxidants
Infections o Viral or bacterial
Drugs o Anti pyretics e.g. - Acetyle salicylic acid
- Phenacetin
o Anti-microbial e.g.- Sulpha ,Chloramphenical ,Nitrofurantion
o Anti-malarial e.g. Primaquine
o Anti tuberculous e.g. Para amino salsylic acid , isoniazid
Genetic variants
Types A+ & B+ o Normal variants.
Type A- o American type (enzyme activity = 5-15%).
Mediterranean type o Severe deficiency (enzyme activity < 5%).
Canton type.

Page | 84

Clinical picture
A. Acute hemolytic anemia
- Features of acute hemolysis without organomegaly (see before).
- Occur 2- 3 days after exposure to the oxidant trigger.
- Degree of hemolysis varies with the triggering agent and the severity of
G6PD enzyme deficiency
- Episodes usually brief as newly produced young RBCs have a higher enzyme
activity that can withstand oxidant stress
- May occur in the neonatal period o neonatal anemia & jaundice.
B. Chronic non spherocytic hemolytic anemia
- Extremely rare.
- Presents with pallor, tinge of jaundice and mild splenomegaly.
Investigations
1. For anemia o Low Hb% and Ht value.
2. For acute hemolysis o Evidence of p RBCs survival and n Erythropiosis.
3. For the cause:
i. Blood film
Fragmented RBCs Heinz bodies

Reticulocytosis Denatured hemoglobin
Appear as purple blue intracellular
inclusion bodies visible with
supravital stains
ii. G6PD Enzyme assay
Done few weeks (2-4 weeks) after the acute attack
During the acute attack, the bone marrow produces young RBCs with
higher enzymatic activity which may give false normal results.
Treatment
A. During the attack
Resuscitation: Ensure ABC
Packed RBCs transfusion (5-10 ml/kg) for severe attack (Hb < 7 gm/dl or < 9
gm/dl with persistent hemoglobinuria).Can be repeated
Control triggers e.g. infection, stop oxidant agent
In a neonate: treatment of associated neonatal jaundice

Page | 85
B. After the attack

- Avoid oxidant food & drugs.
- Anti oxidant o vitamin E.
- Offer screening of other sibling boys
- Offer a card with diagnosis that include forbidden and alternative drugs (e.g.
Anti pyretics in fever o paracetamol or ibubrufen) and avoided foods

Page | 86
Chronic Hemolytic Anemia

Causes
A. Intra corpuscular causes
1. Membrane defects - Hereditary spherocytosis
- Hereditary elliptocytosis (ovalocytosis)
2. Hemoglobinopathy - D thalassemia
- E thalassemia.
- Sickle cell disease
3. Enzymatic defects - Pyruvate kinase deficiency
1. Immunologic (Coombs +ve): Autoimmune hemolytic anemia (Warm type)
2. Non immunologic (Coombs –ve): Hypersplenism
General clinical features
a. Initially
1. Features of progressive Anemia (pallor, fatigue,...)
2. Tinge of jaundice :
- Indirect hyperBilirubinemia ; lemon yellow color
- Normal colored urine (acholuric jaundice)
b. In advanced and neglected cases
1. Skeletal changes due to bone marrow expansion:
* Head (Mongloid features):
Macrocephaly.
Depressed nasal bridge.
Prominent maxillae.
Prognathism.
* Generalized osteoporosis.
2. Splenohepatomegaly due to extramedullary hematopioesis & hemosiderosis
3. Gall bladder Stones (Calcium bilirubinate) in chronic hemolysis for > 4 years.
c. Hematologic crises
1. Aplastic crisis (Erythroblastopenic crisis)
x Transient bone marrow hypoplasia

x Due to parvo-B19 infection (infect erythroid cells).
x Clinically:
Increased pallor without deepening of jaundice
Reticulocytopenia

Page | 87

2. Megaloblastic crisis due to folate deficiencyo aggravation of anemia
3. Hemolytic crisis
Increased rate of hemolysis precipitated by infection
Increasing pallor, jaundice , reticulocytic count
Hemoglobinuria
4. Hyperhemolytic crisis due to associated G6PD deficiency
General Investigations
1. Anemia
* Low Hb% and Ht value
* Usually normocytic normochromic but may be:
- Macrocytic due to associated folate deficiency or marked reticulocytosis
- Microcytic in thalassemia and chronic hemoglobinuria
2. Decreased RBCs survival
* nUnconjugated bilirubin (usually < 5 mg/dl)
* Iron buildup: Ĺ6HUXPLURQDQGIHUULWLQ
3. Increased erythropoiesis
* Modest reticulocytosis ;peaks in hemolytic and hyperhemolytic crises
* Skull X-ray: shows
(Hair on end appearance).
Marrow space expansion
Wide diploic space
Macrocephally
* Bone marrow aspirate: shows

Erythroid hyperplasia
May be megaloblastic in
associated folate deficiency
May be aplastic in aplastic
crisis or PNH
4. p Chromium (51Cr) labelled RBCs survival:

Direct evidence of short RBCs survival (research tool only)

Page | 88

Specific investigation
1. Coombs test: Diagnose Immunologic hemolytic anemia.
2. Blood film for abnormal RBCs morphology e.g.
a. Target cells
RBCs with central staining, a ring of pallor,
and an outer rim of staining seen in
Thalassemia
Sickle cell disease
Hyposplenism
Obstructive liver disease
Iron-deficiency anemia
b. Sickle cells
Seen in sickle cell anemia
c. Microspherocytes
Small spherical cells with loss of central pallor
, Seen in
Hereditary sherocytosis
Immune hemolytic anemia
Hypersplenism
Burn
Sickle Cell disease
3. Osmotic fragility test/auto hemolysis test for Hereditary spherocytosis

4. Flow cytometry for PNH (Ham test is no longer used)
5. Hb electrophoresis for hemoglobinopathies

Page | 89
Hereditary Spherocytosis
(Familial acholuric jaundice)
Pathogenesis
x The most common inherited hemolytic anemia in northern
Europeans
x Autosomal dominant disorder
x Due to deficiency of red cell cytoskeleton proteins(Ankyrin
or Spectrin or protein 4.2)
n Cell wall permeability to Na+ Release of micro vesicles
n Intracellular Na+ influx
n Water content inside RBCs
Cells become spherical with more rigid and less deformable

Premature RBCs aging (over work of Na/K pump)
Exposure to stressful splenic circulation (low pH, low glucose,

high oxidants, high macrophage contact )
RBCs are trapped and destroyed in the spleen.

Page | 90

Clinical picture
* Some patients may go through life with no symptoms
* Positive family history is present in 75% of symptomatic cases
1- Features of anemia starting early in life; 50% present by
2- Features of chronic hemolysis neonatal anemia and jaundice.
3- Gall stones are seen in 50% of unsplenctomized cases by 4-5 years
Investigations
1. For anemia o pHb% and pHt value ( usually normocytic anemia)
2. For chronic hemolysis o p RBCs survival & n erythropoiesis.
3. For the cause:
a. Blood film o RBCs are small, rounded without
central pallor i.e. spherocytes.
b. Negative Coombs’ test rules out autoimmune
hemolytic anemia as a cause of spherocytes in blood
film.
c. Incubated osmotic fragility test:
Test is non-specific ;miss up to 20% of cases
Normally when red cells are placed in solutions of increasing
hypotonicity, it takes in water, swell, and eventually lyses.
Spherocytes (already swollen cells) lyse more readily than normal
biconcave cells
In equivocal results ; perform incubated osmotic fragility test (incubate for
24 hours at 37 0C)
Hemolysis is partially corrected by addition of glucose
d. Flow cytometric EMA (Eosin-5- Maleimide) binding test and the
cryohemolysis test are much more sensitive and specific


Page | 91
Medical treatment
1- Supportive o folic acid 1mg/day (till splenectomy is done)
2- Slight anemia (Hb > 10 gm/dl & reticulocytic count < 10%) o follow up
3- Severe anemia requires packed red cells transfusions.
Elective splenectomy:
Indications ĺ Moderate to Severe anemia
ĺFrequent crises
ĺPoor growth
ĺCardiomegaly
Value : Clinical cure o prevent hemolysis, crises and gall bladder stones
Timing : It is best to postpone splenectomy until after 6 years to avoid
overwhelming fatal infections
Risks : Increased risk of overwhelming infections, particularly
encapsulated organisms
Precautions A. Vaccinate 2–3 weeks before splenectomy for:
Pneumococcal polysaccharide vaccine; repeated every 5
years
Meningococcal group C vaccine
Influenza vaccine; repeated annually
Haemophilus influenzaetype B (Hib) vaccine
B. Long-term penicillin V 250mg 12-hourly (or erythromycin)
C. Aggressive treatment for any febrile illness
N.B: Often, concomitant cholecystectomy should be performed if

there are gallstones detected in pre-operative abdominal ultrasound.

Page | 92
Paroxysmal Nocturnal Hemoglobinuria
Etiology
* Acquired hemolytic anemia where RBCs are susceptible for complement
damage
* Hematopoietic stems cells membranes lack decay accelerating factor (CD55)
and CD59 which are involved in complement degradation
* Absence of CD55 and CD59 o uncontrolled hemolytic action of complement
* Anemia is chronic with acute exacerbations
Clinical picture
* Features of intravascular hemolytic anemia with hemoglobinuria especially
after sleep by night
* Attacks of abdominal and back pain due to micro thrombi
* Complications
- Venous thrombosis
- Iron deficiency
- Aplastic anemia
Investigations
A. General investigations for intravascular hemolysis
B. Specific: Flow cytometric analysis of red cells with anti-CD55 and anti-CD59
Treatment
1. Blood transfusions (Leucocyte-depleted blood to prevent transfusion reactions)
2. Eculizumab
- A recombinant humanized monoclonal antibody that prevents the cleavage
of C5 (and therefore the formation of the membrane attack complex).
- It reduces intravascular hemolysis, hemoglobinuria, the need for transfusion
- Given IV every 2weeks
- Very expensive
3. Long-term anti-coagulant prophylaxis for patients with deep venous
thrombosis
4. Folic acid 3mg daily
5. Bone marrow transplantation

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Thalassemia
Definition: Autosomal recessive disorders due to defective globin chain production
A. D thalassemia syndromes
Impaired D chain production
Due to deletion of one or more of the 4 D globin genes on chromosome 16
1. One gene missing o Silent carrier (Asymptomatic)
2. Two gene missing o D thalassemia trait
- Familial microcytic anemia ; commonly mistaken as iron deficiency
- Normal iron indices
- Normal Electrophoresis for age.
- Diagnosed by DNA analysis.
3. Three genes missing o Hemoglobin H disease
- Mild to moderate microcytic hemolytic anemia at birth
- Evidence of chronic hemolysis
- Electrophoresis shows: Hb H (4E chains).
4. Four genes missing o Fetal hydropes
- Severe intra uterine anemia and anemic heart failure
- Resulting in death in-utero or short after birth
- Electrophoresis shows: Dominant hemoglobin Bart (4 J globin chains )
with complete absence of normal fetal and adult hemoglobin
B. E-thalassemia syndromes
Impaired E chains production
Due to mutation of one or more of the 2 E globin genes on chromosome 11
A. One gene mutation o E thalassemia trait ( Heterozygous E-thalassemia)
Microcytic anemia with no evidence of overt hemolysis
Differentiated from iron deficiency anemia by
R Normal iron indices and Mentzer index <13
R Characteristic hemoglobin electrophoresis:
¾ Hb A2 up to 3-7% in over 90% of cases.(diagnostic)
¾ HbF up to 1-3% in only 50% of cases.
B. Two genes mutation o E thalassemia major
C. Thalassemia intermedia
- Due to a combination of homozygous mild E and D thalassemia
- Moderate anemia (Hb 7–10 g/dL) doesn’t require regular transfusions

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E Thalassemia Major
(Cooley’s anemia)
The commonest chronic hemolytic anemia in Egypt & Mediterranean areas.
Pathophysiology
A. Impaired E chain production
p Production of Deposition of excess Compensatory

HbA (D2 E2) unmatched D chain production of other Hb
inside the RBCs o containing non Beta
hemolysis chains especially Hb F
(D2J2)
Anemia nHbF (nO2 affinity)
Tissue hypoxia
Compensatory increased RBCs production
Medullary hematopoiesis Extra medullary

hematopoiesis
Bone marrow expansion Splenomegaly (r

(Skeletal changes) hepatomegaly)
+ hypersplenism
B. Iron overload due to

- Chronic hemolysis.
- Enhanced iron absorption.
- Repeated blood transfusion.

Page | 95
Clinical picture
A. General features of chronic hemolytic anemia (see before)
Manifestations start insidiously after the 6th month of age when switch from
J to E chain production usually normally occur.
Classic features: Progressive anemia, jaundice ,thalassemic facies,and
organomegaly
B. Hemosiderosis o Iron deposition in:

Skin Pituitary
Bronzed skin Short stature
Hypogonadism
Heart
Restrictive cardiomyopathy
Dysrhythmias Thyroid and parathyriod
Heart failure Hypothyroidism
Hypoparathyriodism
Liver
Liver cirrhosis
Liver cell failure
Hepatitis Gonads
Hypogonadism
Pancreas
Delayed puberty
1. Diabetes mellitus
C. Complications and causes of death
1. Heart failure
4. Hypersplenism :
R Pallor, purpura,
pyrexia, and
organomegaly
2. Liver cell failure R CBC: pancytopenia
R Bone marrow:
marrow hyperplasia ,
no malignant cells
3. Diabetic keto acidosis
5. Frequent blood transfusions carry risk of

blood bone infections e.g. HBV, HCV, AIDS, and CMV

Page | 96
Investigations
a. For anemia o Low Hb% and Ht. value.
b. For chronic hemolysis “Hair on end”
Unconjugated hyperbilirubinemia appearance
Reticulocytosis (commonly <8%)
Skull X-ray in children >3 years
c. For the cause
1- Blood film o hypochromic, microcytic anemia with target cells.
2- Alkaline denaturation (Apt) test o Hb F resist denaturation by alkali
3- Hemoglobin electrophoresis:
Markedly raised Hb F (80-90%)
Slightly raised Hb A2
Absent or near absent Hb A
4- Prenatal diagnosis is possible by chorionic villous sampling (CVS)
d. For diagnosis of iron overload
Serum iron and ferritin
Cardiac / hepatic MRI*
Liver biopsy*
Liver iron by Superconducting Quantum Interference Device (SQUID)
Treatment
1. Chronic transfusion therapy
x Indications for initiation of regular red cell transfusions include:
Hemoglobin level 7 g/dl (on at least 2 measurements)
Poor growth
Facial bone changes
x Aim: To keep pre transfusion Hb > 9.5- 10.5 gm/dl
x Dose: 10-15 ml/kg packed RBCs monthly.
x Benefits
Allow normal growth and activity
Decreases bone marrow activity o p skeletal changes.
Decreases extra medullary hematopoiesis o p organomegaly.
2. Iron chelation therapy
x Often deferred until age 3 to 4 years.
x Indications:
Cumulative transfusion load of 120 ml/kg or greater
Serum ferritin level persistently >1,000 ng/ml
Liver iron concentration .5–7 mg/g dry weight

Page | 97
x Drugs used
A. Desferroxamine (Desferal)
Dose: 25-50 mg/kg/day
Route: IV or by continuous SC pump for 10 hours, 5-6 nights per week.
Side effect: anaphylaxis, deafness, cataract, retinal damage , yerssinia
sepsis and skeletal changes
Ascorbic acid 200 mg daily enhance the chelating effect of Desferal
B. Recent Oral drugs
1. Deferiprone (Ferriprox)
Dose : 75-100 mg/kg
Value: Effective in Reducing cardiac iron overload.
Side effects: Gastric upset ,neutropenia and agranylocytosis
2. Defrasirox (Exjade)
As effective as desferal but oral with longer half life
Once daily, 20-40 mg /kg
Monitoring of liver enzymes and serum creatinine is essential
3. Supportive treatment
Low iron diet
Folic acid 1mg/day
Endorcine support as necessary.
Hepatitis A and B vaccine
4. Splenectomy
x Indications
A. Hypersplenism suggested by:
- Increasing need for transfusion by t 50% than usual for > 6 months.
- Annual PRBCs > 250 ml/kg/year in face of uncontrolled iron overload
- Severe leucopenia and / or thrombocytopenia (Pancytopenia)
B. Huge spleen with pain or pressure symptoms.
x When: Preferably after the 5th – 6th year
x Risk: Overwhelming sepsis (especially if done < 5 years)
x Precautions: See before
5. Other lines of treatment
Hydroxyurea o Induction of Hb F o pUnmatched D chain accumulation
o p hemolysis (of limited value due to serious side effects).
Stem cell transplantation o best for patient less than 17 years
Gene therapy is under research
6. Genetic counseling

Page | 98
Sickle Cell Disease

Etiology
Autosomal recessive disorder.
Due to single amino acid substitution in the number 6 position of the E-chains
(valine for glutamic) resulting in new Hb o HbS (D2E26glut. o D2E26val. = HbS).
Forms
Sickle cell Anemia; SCA o Hb SS ; homozygous
Sickle cell trait ; SCT o Hb AS ; heterozygous
Pathogenesis
HbS can’t withstand hypoxia
If exposed to low O2 tensions
HbS polymerize
RBCs distortion
Intra vascular sickling with subsequent
1. Aggregation o vascular occlusion

2. Trapping and hemolysis in reticulo endothelial system in the spleen & liver
Clinical picture
Common in negroes
Features of anemia
Features of chronic hemolysis Starting after the 6th month of age
Renal disorders o proteinuria, nephrotic syndrome, chronic renal failure.

Page | 99

Crisises
1. Aplastic
2. Hemolytic
3. Megaloblastic
4. Hyperhemolytic (as before)
5. Vaso occlusive crisis ( painful crisis)
Mechanism
In vivo sickling o vascular occlusion o ischemia r infarction.
Reduced Nitric Oxide bioavailability o vasoconstriction and platelet
activation
WBCs counts are often elevated, adhere to endothelial cells and may
further trap sickled red cells, contributing to stasis
Precipitating factors
Fever, Acidosis, Dehydration, Infection & Hypoxia, exposure to cold
Clinically
Acute chest syndrome (ACS):
CNS Due to pulmonary emboli of
o Cerebrovascular stroke necrotic bone marrow (fat emboli)
o Retinopathy infection or pulmonary infarction
Clinical Presentation :
Myocardial infarction Gradual or catastrophic.
Severe respiratory distress
Renal infarction
Chest pain, fever
o Hematuria
Hypoxemia
o Chronic renal failure CBC: Leucocytosis
Hand and foot syndrome: CXR: Lung consolidation.
Ischemia of metacrapal &
Splenic infarctionso fibrosis o
metatarsal bones
shrinkingo autosplenectomy &
Avascular necrosis of bone hyposplenism
e.g. femoral head
Others e.g. leg ulcers, priapism
6. Splenic sequestration crisis
Sudden pooling of the blood in the spleen (r the liver)
Precipitated by dehydration
Occurs primarily in infants
Clinically
Acute pallor and acute abdominal pain
Massive splenomegaly
Hypovolemic shock.
'HFOLQHLQKHPRJORELQRI g/dL from the patient's baseline hemoglobin;
reticulocytosis and a decrease in the platelet count may be present

Page | 100
7. Infectious crisis
Due to hyposplenism (popsonization)
Common organisms: usually encapsulated bacteria
Site
- Meningitis (Pneumococci & H. influenza)
- Pneumonia (Pneumococci)
- Osteomyelitis (Salmonella)
Investigations
1. For anemia o Low Hb% & Ht value.
2. For chronic hemolysis op RBCs survival & n erythropoiesis.
3. For the cause
a) Blood film:
Detect sickle cells in peripheral blood. If not detected, sickling can be
enhanced by adding sodium metabisulfite (Sickling test).
Howell–Jolly bodies (nuclear remnants) and Sub membranous pits in
RBCs may be seen indicating hyposplenism.
b) Hemoglobin electrophoresis: Show HbSS (90%) & Hb F (2-10%).

c) Neonatal screening allows early detection , adequate care and longer
survival
Treatment
1. Avoid factors precipitating painful crisis e.g.
Vigorous hydration during exposure to extreme stress
Vigorous treatment of infections
2. Chronic transfusion therapy & iron chelation (Equivocal)
Indications:
- Stroke
- Recurrent painful crisis.
- Recurrent acute chest syndrome

Page | 101
3. Treatment of crises:
A. Vaso occlusive
Oxygen
Hydration ; oral and IV to maintain euvolemia
Pain control e.g. ibuprofen, acetaminophen, codeine, or morphine
Empirical antibiotics (cephalosporin and macrolide) for infections
Simple transfusion target post transfusion hemoglobin ±10 g/dL
Exchange transfusion program for recurrent cases
B. Sequestration
Blood transfusion, typically 5 mL/kg of packed red blood cells
Exchange transfusion
Prophylactic splenectomy is the only effective strategy for preventing
future life-threatening episodes
C. Aplastic / hemolytic crisis o Blood transfusion
4. Control infection:
Prophylactic penicillin for life
Immunize against: Pneumococci & H. influenza
5. Alternative treatment
* Hydroxyurea
Value
- Induction of Hb F (takes time so not suitable for acute therapy)
- Improve RBCs hydration
- The only effective drug proved to reduce the frequency of painful episodes
Dose: typical starting daily dose is 15-20 mg/kg
* Hematopoietic stem cell transplantation.
Sickle cell trait (Hb AS)

Hemoglobin analysis shows Hb A, typically >50% and (Hb S <50%)
Asymptomatic but complications do exist e.g.
R Sudden death during rigorous exercise
R Splenic infarcts at high altitude
R Hematuria
R Bacteriuria
R Susceptibility to eye injury with formation of a hyphema
R Susceptibility to renal medullary cancer
Patients are resistant to lethal effects of falciparum malaria

Page | 102
Auto Immune Hemolytic Anemia (AIHA)

Definition
Hemolytic anemia due to circulating antibodies against patients own RBCs.
Explanation
- Altered immune response (not recognize self-antigens).
- Altered RBCs antigenicity by infection or drugs.
Clinical types: According to the type of auto antibodies
Causes Warm reactive autoantibodies Cold reactive autoantibodies
Primary 50 % are idiopathic Idiopathic

Secondary
Infection CMV, HBV Mycoplasma pneumonia
Infectious mononucleosis
Vaccination MMR
Disease Leukemia/ Lymphoma. Lymphoma

SLE
Drugs Methyle Dopa, penicillin,

interferon
Criteria of - IgG. - IgM
Antibodies - Active at 37qC - Active at below 37qC
Clinical picture
1. AIHA due to warm reactive autoantibodies
A. Acute transient type B. Chronic type
Acute hemolytic anemia with Chronic hemolytic anemia.
splenomegaly. In child < 2 or > 12 years
In child 2-12 year. May be underlying systemic disease
May follow respiratory infection. e.g. lymphoma.
Responsive to steroids Variable response to steroids.
Lasting 3-6 months Last months and years
2. AIHA due to cold reactive autoantibodies (cryopathic hemolytic syndromes)
A. Cold agglutinin disease

Cold reacting auto antibodies may present in low titer
Exposure to triggering agent e.g. Infection with mycoplasma
Increased auto antibody titer
Eventual chronic hemolytic anemia

Page | 103

B. Paroxysmal cold hemoglobinuria
Due to Donath Landsteiner antibody (IgG which can activate
complement)
Antibodies are biphasic, reacting with red cells in the cold in the
peripheral circulation, with lysis occurring due to complement activation
when the cells return to the central circulation.
The lytic reaction is demonstrated in vitro by incubating the patient’s red
cells & Serum at 4°C and then warming the mixture to 37°C (Donath–
Landsteiner test)
Association:
Infection with mycoplasma, Ebstein Barr virus, Cytomegalo
virus, measles, mumps or chickenpox
Congenital or acquired syphilis.
Course: Mild, resolve with infection resolution.
Investigations
x For anemia o Low Hb % & p Ht value.
x For acute hemolysis (see before)
x For chronic hemolysis (see before)
x For the cause.
1. CBC :
- Micro spherocytes.
- AIHA plus autoimmune thrombocytopenia o Evan’s Syndrome.
2. Positive Coombs test (Antiglobulin test)
- Direct: Detects high titer of autoantibodies coating the RBCs
- Indirect: Detects the free autoantibodies in patient serum
Treatment
A. AIHA due to warm antibodies
1. Mild and asymptomatic anemia needs only follow up
2. Treatment of symptomatic anemia
Prednisolone Splenectomy For refractory cases
2 mg/kg If there is no Anti-CD20
4- 6 mg/kg for profound response to steroids (Rituximab)
hemolysis I.VIG
Reduce destruction of Plasmapharesis
antibody-coated cells
B. Cold agglutinin disease

* Patients should avoid exposure to cold.
* Steroids and splenectomy are usually ineffective.

Page | 104
* Anti-CD20 (Rituximab) has been successful in some cases.

* Plasmapharesis: for severe cases.
C. Supportive care
* Treat the underlying cause
* Blood transfusion:
Value Life saving for severe anemia
Problem Compatibility testing is complicated by the
presence of unspecific red cell autoantibodies
Use Small volume of packed RBCs starting with a
test dose
Use the least incompatible blood
Disadvantage Hard to find totally compatible blood.
Transient effect

Page | 105

Approach to a Case of Anemia
A. History
1. Onset
G6PD, spherocytosis can present from
neonatal period
Thalassemia, sickle cell anemia present
> 6 month
2. Past history
Hemorrhage
Drugs which may induce (aplasia,
acute hemolysis in G6PD deficiency).
Infection or fava beans o G6PD
deficiency.
3. Family history ofor similar cases and consanguinity for inherited causes.
B. Clinical approach : Search for clinical clues of :

1. Bone marrow failure ( Pallor, Purpura, Pyrexia ± organomegaly)
+ +
2. Acute hemolytic anemia
OR +
Triggers Acute pallor/jaundice Dark urine
3. Chronic hemolytic anemia
Gradual pallor/jaundice Organomegaly Complications

Page | 106
4. Anemia with congenital anomalies:
Fanconi anemia. Diamond Blackfan anemia.

5. Anemia with systemic associations
GIT upset (Folic acid deficiency) Neuropathy (B12 deficiency)
C. Laboratory approach
1. Is it anemia? o Ļ+E Ļ+WYDOXH
2. Is there bone marrow failure?
Features Consider Workup

Anemia - Aplastic anemia - Blood film for
Thrombocytopenia
- Leukemia abnormal cells
Leucopenia or increased
WBCs - Bone marrow infiltration - BM examination
- 'RQ¶Wforget hypersplenism
3. Is it microcytic anemia?
Workup
Features - Iron indices ( diagnose iron deficiency and anemia
MCV < 70 fl of chronic illness)
MCH < 27 pg
MCHC < 30% - Blood film for basophilic stippling
- Hemoglobin electrophoresis for thalassemia
- Bone marrow examination for ringed sideroblasts
- Serum lead level

Page | 107

4. Is it macrocytic anemia?
Features : MCV > 85 fl
Causes
Folic acid and B12 deficiency
Other causes:
Aplastic or hypoplastic anemia
Hepatic disease
Hypothyroidism
Drugs: antifolate, cytotoxics
Workup: Consider Serum folic acid and B12 assays and Schilling tests
5. Is it hemolytic anemia?
x Is there increased red cell breakdown?
- Anemia
- nBilirubin: unconjugated, from hem breakdown
- nUrinary urobilinogen (no urinary conjugated bilirubin).
- nSerum lactic dehydrogenase (LDH), as released from the RBC
x Is there increased red cell production?
- Reticulocytosis
x Is the hemolysis mainly extra- or intravascular?
R Extravascular hemolysis may lead to splenic hypertrophy and
splenomegaly
R Features of intravascular hemolysis are:
- n Plasma hemoglobin
- p Haptoglobin & haemopexin(hemoglobin carriers).
- n Metheamalbumin
- n Unconjugated bilirubin, fecal and urinary urobilinogen
- Hemoglobinuria (and heamosiderinuria)
- n Serum LDH
Causes : See classification of anemia
Workup:
Positive Coomb’s test: Immune hemolytic anemia
Negative Coomb’s test : Other causes of hemolytic anemia:
Consider
Osmotic fragility and autohemolysis tests
Enzyme assays e.g. G6PD deficiency
Blood film and sickling tests
Electrophoresis

Page | 108
Hemorrhagic disorders
Hemostasis is the mechanisms of stoppage of bleeding after injury of a blood
vessel
I. 1ry Hemostatic Mechanisms
a. Vascular factor
Role
Reflex vasoconstriction at the site of
bleeding.
Damaged endothelium release serotonin
and activate F XII
Assessment
Bleeding time.
Hess test
b. Platelets
Criteria
Life span: 8-10 day
Count: 150- 400.000 platelets per ml
Mean platelet diameter: 1- 4 PM
Distribution: one third (30%) in the spleen; two-thirds in the bloodstream
Controlled by thrombopeiotin
Role
1. Adhesion to exposed collagen fibers (Von Willbrand factor is essential).
2. Aggregation; platelets accumulate at injured site helped by adenosine
diphosphate (ADP) & thromboxane A2(TXA2)
3. Release of:
Thromoxane A2 on platelet aggregation.
Serotinin on vasoconstriction
Platelet factor 3 (PF3) o enhance clotting
Thrombasthinine on clot retraction.
4. Platelet plug formation
Assessment
Bleeding timeo normal = 4-8 min.
Hess test (capillary fragility test) o cuff of sphygmomanometer is
inflated between systole & diastole for 5 min.o if > 5 petechiae appear
within 5 cm circle in the forearm o +ve test.
Platelet count (N = 150 – 400.000 /mm3)
Platelet function tests whenever thromocytopathy is suspected
- Assess platelet adhesiveness and aggregation.
- Assay of PF3 level.
- Clot retraction test.

Page | 109

II. Coagulation factors
Criteria
Most coagulation factors are formed in the liver and circulate in an inactive
form (Pro coagulants) which are activated in a cascade manner
Vitamin K dependent factors o II, VII, IX, X.
Most activation reactions occurred on the surface of the platelets
Calcium is a cofactor for many steps of activation cascade ;particularly the
common pathway
Activation cascade
Intrinsic pathway Extrinsic pathway
Damaged surface (exposed collagen) Trauma
Tissue
Kininogen thromboplastin
Kallikrein
XII XIIa VIIa VII
XI XIa
IX IXa
VII VIIIa
Common pathway
X Xa X
Platelet factor 3 Platelet factor 3
Calcium ,Factor V Calcium ,Factor V
Prothrombin Thrombin
Thrombasthenin XIIIa
Stable clot Fibrin polymers Fibrin monomers Fibrinogen

Page | 110
Coagulation factors names

I Fibrinogen II Prothrombin
III Tissue thromboplastin IV Calcium
V Labile factor VII Stable factor
VIII Anti-hemophilic factor IX Chrismas factor
X Stuart Prower factor XI Plasma thromboplastin antecedent
XII Hageman factor XIII Fibrin stabilizing factor
Others : High Molecular Weight Kinonogen , Kallekrein
Assessment:
1. Clotting time o normal = 8-12 min.
rough test o prolonged with defects in any phase
2. Thrombin time (TT) o normal = 15-20 Sec.
Time needed to plasma to clot after addition of bovine thrombin
Prolonged in fibrinogen deficiency.
3. Prothrombin time (PT) o normal = 12-14 Sec.
Time needed to plasma to clot after addition of thromboplastin &
Calcium.
Test extrinsic & common pathways.
4. Partial thromboplastin time (aPTT) o normal = 25-40 Sec.
Time needed for plasma to clot after addition of kaolin, Calcium &
platelets.
Test intrinsic & common pathways.
Interpretation
Defect in PT PTT Specific
Common pathway Prolonged Prolonged
(X,V,II,I)
Extrinsic pathway Prolonged Normal Specific factor assay
(VII)
Intrinsic pathway Normal Prolonged
(XII,XI,IX,VIII)
N.B: Prolonged both PT & PTT also occur in multiple factors deficiency e.g.
Liver cell failure
Vitamin K deficiency
Disseminated Intra vascular Coagulation (DIC)
5. Specific tests e.g. Von Willbrand disease:
Prolonged both bleeding time and clotting time
Decreased both F VIIIc & F VIIIa
Von Willbrand factor assay

Page | 111
Control of coagulation factors

1. Natural coagulation inhibitors
Value: localizes thrombosis to the site of injury.
a. Antithrombin (AT)
- Potent inhibitor of factors XIa, IXa, Xa, and thrombin.
- Its action is greatly potentiated by heparin.
b. Activated protein C
- Vitamin K dependent protein
- Activated by thrombin
- Activated protein C inactivates factor V and factor VIII
c. Protein S
- This is a cofactor for protein C
2. Fibrinolytic system: (Fibrinolysis)

Plasmin is generated from its inactive precursor plasminogen
This is achieved principally via tissue plasminogen activator (t-PA) released
from endothelial cells.
Some plasminogen activation may also be promoted by urokinase, produced
in the kidneys (u-PA).
Plasmin breaks down fibrinogen and fibrin into fragments X, Y, D and E,
collectively known as fibrin (and fibrinogen) degradation products (FDPs).
D-dimer is produced when cross-linked fibrin is degraded.
Fibrinolysis helps to restore vessel patency after vascular damage.
Plasminogen activators (t-PA ,u-PA)

F XIIa and FVIIa
Plasminogen Plasmin
Fibrin Fibrin degradation products

Fibrin cross links products(D-Dimer)

Page | 112
Purpura
Definition: Group of disorders characterized by:
1- Multiple, spontaneous hemorrhages in the skin and mucous membranes.
2- Range from pin point (petechiae) to several centimeters (ecchymosis)
3- Petechiae are purple in color, not elevated, do not blanch on pressure, not pruritic
Possible bleeding sites:
Skin: petechiae, ecchymosis
Mucous membranes: oral, gingival, conjunctiva,..
Orificial: epistaxis, hemoptysis, hematuria, melena..
Internal: intracranial, retinal, pleural, pericardial,..
Causes
I. Non thrombocytopenic purpura: (Normal platelet count)
1. Vascular purpura
a. Hereditary: e.g.
Ehler Danlos Syndrome
Defect in type III collagen in
connective tissue.
Clinical picture
Hypermobile joints
Purpura
b. Acquired
Vasculitis
Henoch schonlein purpura
Sepsis (meningeococcal).
Weak blood vessels
Scurvy o defective connective tissue collagen.
Cushing syndrome
2. Thrombasthenia (Platelet dysfunction; Thrombocytopathy)
a. Hereditary thrombocytopathy
Defective adhesion: Von Willbrand disease , Bernard Soulier disease
Defective aggregation: Glanzmann disease.
b. Acquired
Uremia (Renal failure)
Cholemia (Liver failure)
Drug induced: Aspirin (p ADP & Thromboxan A2),Heparin
Autoimmune: SLE

Page | 113
II. Thrombocytopenic purpura

Defined as platelet count <100.000/mm3
A. Decreased production
With decreased marrow megakaryocytes
I. Congenital
1. Fanconi anemia
2. Thrombocytopenia absent radii (TAR)syndrome
Thrombocytopenia
Absent or hypoplastic radii
Other associated anomalies e.g. congenital heart disease
3. Wiskott – Aldrich syndrome

Sex linked recessive disorder
Microthrombocytopenia
Infantile eczema and bloody diarrhea are the commonest presentation
Combined immunodeficiency
Petechiae due to Eczema Pneumonia and other

thrombocytopenia infections
II. Acquired
1. Aplastic anemia
2. Bone marrow infiltration (e.g. Leukemia).
3. Advanced megaloblastic anemia

Page | 114
B. Increased destruction
With compensatory increased marrow megakaryocytes
I. Immunologic
Primary : Idiopathic thrombocytopenic purpura
Secondary to
Immunologic diseases e.g. SLE
Post transfusion purpura
Drug induced e.g. Heparin, Phenytion
Malignancy e.g. Lymphoma
II. Non immunologic
Microangiopathic hemolytic anemia e.g. DIC, hemolytic uremic
syndrome.
Hypersplenism.
Acute infections, Sepsis.
Thrombotic thrombocytopenic purpura
Kasabach-Merritt syndrome (KMS):
Combination of giant cavernous hemangioma, thrombocytopenia,

and coagulopathy
Platelets are trapped and destroyed in the giant cavernous
hemangioma
Frequently associated with disseminated intra vascular coagulation
Treatment : steroids ,interferon, surgical ligation of feeding vessels

Page | 115
Idiopathic Thrombocytopenic Purpura (ITP)

(Immune Thrombocytopenic Purpura
Definition: Purpura characterized by:
- Shortened platelets survival due to antiplatelet antibodies
- Thrombocytopenia (< 100.000 /mm3).
- Increased bone marrow megakaryocytes.
- Absent other identifiable thrombocytopenic disorders (a diagnosis of exclusion).
Pathophysiology
Anti-platelets antibodies triggered by preceding viral infection
Antibodies coated platelets is trapped in the spleen by macrophage Fc receptors
Spleen is the primary site for antibody production and platelets destruction.
Clinical picture
Incidence
- Age: peak between 1 – 4 years
- Sex incidence: Equal
Acute purpura
R The classic presentation of ITP is a previously healthy 1-4 yr old child who
has sudden onset of generalized petechiae and purpura.
R The parents often state that the child was fine yesterday and now is covered
with bruises and purple dots.
R Often there is bleeding from the gums and mucous membranes, particularly
with profound thrombocytopenia (platelet count <10 × 109/L).
R There is a history of a preceding viral infection 1-4 wk before the onset of
thrombocytopenia in 50-60% of patients.
Important exclusions
1. No significant
organomegaly ;however
tip of the spleen is
palpable in 10 % of
cases
2. No significant pallor
except with severe
bleeding or associated
autoimmune hemolytic
anemia (Evans
syndrome)

Page | 116

Clinical classification of bleeding severity
1 No symptoms
2 Mild symptoms:
Bruising and petechiae
Occasional minor epistaxis
Very little interference with daily living
3 Moderate:
More severe skin and mucosal lesions
More troublesome epistaxis and menorrhagia
4 Severe:
Bleeding episodes: menorrhagia, epistaxis, melena—requiring
transfusion or hospitalization
Symptoms interfering seriously with the quality of life
(Nelson textbook of pediatrics, 2016)
Diagnosis
Isolated thrombocytopenia in healthy child with normal blood smear
Blood smear:
- Platelet count o always < 100.000 / mm3; platelets usually large sized
- Normal WBCs and RBCs (except in Evans and severe bleeds); no abnormal
cells
Bone marrow examination
- Increased numbers of megakaryocytes, many of which appear immature
- Normal myeloid and erythroid cells
Indications for bone marrow examination include
1. Abnormal WBC count or differential
2. Unexplained anemia
3. History and physical examination suggestive of a bone marrow failure
syndrome or malignancy.
4. No response to supportive therapy and steroid therapy needs to be started
Blood smear Bone marrow smear

Page | 117

Other tests
A direct Coombs should be done if there is unexplained anemia to rule out
Evans syndrome or before instituting therapy with IV anti-D.
In adolescents, an antinuclear antibody test should be done to evaluate for

SLE.
HIV studies should be done in at-risk populations, especially sexually active
teens.
Platelet antibody testing is seldom useful in acute ITP.
Prognosis
Spontaneous resolution occurs in 80 % of children with acute ITP within
6 mo.
About 20% of children with acute ITP go on to have chronic ITP.
Fewer than 1% of patients develop an intracranial hemorrhage
Therapy does not appear to affect the natural history of the illness. There is
no evidence that therapy prevents serious bleeding.
The prognosis may be related more to age, as ITP in younger children is
more likely to resolve whereas the development of chronic ITP in
adolescents approaches 50%.
From other causes of purpura :
ITP BM aplasia BM infiltration Hypersplenism
Clinical Isolated Purpura Purpura Purpura
purpura in Pallor Pallor Pallor
clinically Pyrexia Pyrexia Pyrexia
well child No organomegaly Organomegaly Splenomegaly
Blood film pPlatelets Pancytopenia Pancytopenia Pancytopenia
Bone Megakaryocyte Hypoplastic Infiltrated Hyperplastic
Marrow hyperplasia

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Treatment of ITP
I. No therapy (Observation)
x For patients with minimal, mild, and moderate symptoms
x Education and counseling of the family about benign nature of ITP
x Avoid trauma, aspirin, contact sports.
II. Drug therapy
- Indicated for significant bleeding with platelet counts below 20 × 109/L
- Aim : to raise platelets above theoretically safe level >20 × 109/L
1. Prednisone
Decrease platelet antibodies production and phagocytosis of antibody coated platelets
Standard dose: 2 mg /kg/day for 21 days o gradually tapered
High dose :4 mg / kg/day for 4 days o less steriod side effects
Two thirds will respond but relapse is common
Standard dose : response in 1 week
High dose : platelets > 20× 109/L in 2 days , platelets > 50× 109/L in 3-4 days
4. Rituximab*
Anti-platelets
Auto anti-bodies 5.splenectomy*
Auto reactive B CD 20 Pre B
lymphocytes lymphocytes
Spleen
Macrophages
With Fc receptors
Trapping antibody coated
platelets
2. Intravenous Immunoglobulin (IVIG) 3. intravenous anti D (Win Rho)

Block macrophage Fc receptors o Coat Rh positive RBCs o RBC-antibody
protect platelets from destruction complexes bind to macrophage Fc receptors o
Dose : 0.8-1 gm/kg for 1- 2 days platelet escape destruction with transient mild
Induces a rapid rise in platelet hemolysis (Patient must be unsplenctomized, Rh
count (usually >20 × 109/L) in positive , with Hb > 9 gm/dl)
95% of patients within 2 days Should not be used with IVIG
Very useful in serious bleeding or Dose : 50-75 μg/kg
urgent surgery Causes a rise in platelet count to >20 × 109/L in
85% of patients within 48-72 hr

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* Splenectomy
Indications - Severe ITP with life threatening bleeding unresponsive to
steroids and intravenous immunoglobulin
- A second line therapy for Chronic ITP uncontrolled medically
Response - Two-thirds will achieve a normal platelet count
* Rituximab
Nature Anti CD20 monoclonal antibody
Role Deplete auto reactive B cells (mainly for chronic ITP)
Treatment of life threatening bleeding (e.g. intracranial hemorrhage):

1. Resuscitation (including blood transfusion if needed)
2. Platelet transfusion (especially if platelets count < 20.000/mm3).
* Have shorter life span but can be life saving in life threatening
hemorrhage or in case of emergency operation e.g. splenectomy
* Dose: 0.2 platelet units per kg as a bolus followed by continuous
infusion if required
3. I.V. immunoglobulin 1gm/kg/day for 2-3 days.
4. I.V. methyleprednisolone 30 mg / kg/day for three days
5. Emergency splenectomy (not usually recommended).
6. Recombinant human factor VIIa (Rhu VIIa)
7DNHKRPHPHVVDJHV
x There are no data showing that treatment affects
either short- or long-term clinical outcome of ITP
x Platelet transfusion in ITP is usually contraindicated
unless life-threatening bleeding is present
(Nelson Textbook Of Pediatrics, 2016 )

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Anaphylactoid Purpura (Henoch Schonlein Purpura)
Definition
x The commonest vasculitis of childhood
x Characterized by immunoglobulin (Ig) A deposition in the small vessels
mainly in the skin, joints, gastrointestinal tract, and kidney.
x Peak age incidence between 2-8 years ; more in males
x May follow drugs or upper respiratory viral or bacterial (sterptoccoci) infection
Clinical picture
1. Skin rash
In 100 % of cases
Skin lesions are usually symmetric and occur in gravity-dependent areas
(lower extremities) or on pressure points (buttocks and extensor surfaces)
Start as palpable erythematous maculopapular rash then become purpuric
(petechiae).
May be pruritic.
Association: Non pitting angioedema of hands, feet, lips, scalp
Typical HSP rash Angio edema of dorsa of hands

2. Arthritis/arthralgia
In 75 % of cases.
Oligoarticular usually in large joints e.g. ankle & knee.
Swollen, hot, tender, with limitation of movement.
Usually resolves within 2 wk but can recur without residuals
Swollen ankles with typical HSP rash, and angio

edema of dorsa of feet

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3. Gastro intestinal tract manifestations

In 80% of cases
Presentations
Vomiting, diarrhea, paralytic ileus
Bowel angina (postprandial abdominal pain, bloody diarrhea)
Complications
Intussusception (? due to submucosal hematoma)
Bowel infarction and perforation
4. Renal
Mainly Rarely
- Hematuria - Proteinuria
- Acute nephritis - Nephrotic syndrome.
- Normal renal function - Chronic renal disease develops in 1-2% of
children with HSP, and approximately 8% of
those with HSP nephritis go on to have end-
stage renal disease.
5. Others vascultic manifestations
Neurological o seizures, paresis.
Testis o Hemorrhage.
Diagnosis
¾ The diagnosis of HSP is a clinical one
¾ No laboratory finding is diagnostic of HSP
1. For purpura :
Normal platelet count & function (may be thrombocytosis) .
Normal coagulation profile.
2. For renal manifestations
Urine analysis for o RBCs, RBCs casts, proteinuria
Renal function tests
Renal biopsy for renal insufficiency or heavy proteinuria
3. For gastro intestinal manifestations
Stool analysis for gross or occult blood
Abdominal ultrasound and/or abdominal CT for intussusception
4. Others
Increased ESR and serum IgA
Biopsies of skin and kidney
Can give diagnostic clue, particularly in atypical or severe cases
Shows characteristic leukocytoclastic vasculitis with intramural
granulocytes in small arterioles and/or venules with deposits of IgA

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Treatment
1. Symptomatic and supportive care e.g. bed rest for joint pain
2. Medications :
Anti-inflammatory medicines e.g. ibuprofen or painkillers e.g. paracetamol
may help relieve some of the joint pain
Empiric use of prednisone (1 mg/kg/day for 1 to 2 wk, followed by taper)
Evidence exist to support use of steroids for bowel angina(Reduces
abdominal pain) and neurological manifestations
It does not alter overall prognosis nor prevent renal disease
3. Follow up
It is recommended that children with HSP undergo serial monitoring of
blood pressure and urinalyses for 6 mo after diagnosis, especially those who
presented with hypertension or urinary abnormalities.

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Coagulation Disorders
A. Hereditary
1. Intrinsic pathway disorders:
- Factor VIII deficiency (Hemophilia A)
- Factor IX deficiency (Hemophilia B or Christmas disease).
- Factor XI deficiency (Hemophilia C).
- Factor XII deficiency
- Von Willbrand disease (Vascular hemophilia) commonest disorder.
2. Extrinsic pathway disorders

- Factor VII deficiency
3. Common pathway disorders:

- Factors II, X deficiency
- Factors V (Para Hemophilia)
- Fibrinogen deficiency:
- Congenital afibrinogenaemia.
- Congenital dysfibrinogenaemia
- Factor XIII deficiency
B. Acquired
1- Vitamin K deficiency
* Hemorrhagic disease of newborn: see neonatology
* Vitamin k malabsorption due to:
- Biliary atresia / obstruction
- Fat malabsorption e.g. celiac disease,
* Vitamin K antagonists
2- Liver cell failure
3- Disseminated intravascular coagulation (DIC).
4- Others:
- Massive transfusion syndrome
- Medications: heparin , thrombolytics , L-Asparginase
- Inhibitors of coagulation due to:
a. Hemphelia inhibitors
b. Auto immunes diseases : SLE , rheumatoid arthritis

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Hemophelia A (classic hemophelia)
Definition
Sex-linked recessive coagulation defect due to deficiency of factor VIII-C
20% of cases are new mutations.
Hemophilia A represents 80% of all hemophiliacs
Pathophysiology
Factor VIII-C is synthesized by the liver and reticuloendothelial system
In plasma, factor VIII-C is stabilized and protected from degradation by Von
Willebrand factor(vWF) protein
In the presence of normal vWF, the half-life of factor VIII-C is
approximately 12 hours, whereas in the absence of vWF, the half-life of
factor VIII-C is reduced to 2 hours
(Illustrated peadiatrics ,Tom Lissauer )

Pattern of deficiency
- Hemostatic level of F VIII-C is >30- 40U/L (30-40%); below which bleeding occur
- Plasma level of Factor VIII-C in carrier females is between 30-50 %
Clinical picture
Severity of bleeding episode is dependent on the plasma level of factor VIII-C and the
severity of trauma
Severe disease Moderate disease Mild disease
F VIII-C < 1% 1-5% 5-25%
Bleeding Bleed Bleed with minor Bleed with severe
trigger spontaneously trauma trauma

Page | 125
1. In neonate
Unusual bleeding from the
circumcision site or umbilical stump
2. External bleeding
e.g.
Epistaxis
Dental /mouth bleeding
GIT bleeding
Hematuria
3. Skin bleeding
Easy bruising
Ecchymotic patches
Hematomas
No petechaie
4. Hemarthrosis
The hallmark of hemophilia A and B
Affects mainly the big joints of the
lower limbs
Affected joint become swollen, red,
hot, and tender with limited mobility
Tend to be recurrent
Recurrent hemarthrosiso joint
fibrosis / ankylosis & muscle atrophy
5. Internal bleeding
e.g.
Muscle hematoma
Intracranial
Retroperitoneal
Hemothorax

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Investigations
1. For diagnosis
Prolonged Normal
Clotting time Bleeding time
Prolonged aPTT Normal PT
F VIII-C assay o Low (Diagnostic)
2. For carrier detection

Direct F VIII-C gene mutation analysis.
3. For prenatal diagnosis
Chorionic villous sample or amniocentesis and gene mutation analysis.
Fetal blood sampling o immunoradiometric assay of F VIII-C antigen
Treatment
1. Primary prophylaxis
Regular F VIII replacement 20 unit/kg 3 times a week
The National Hemophilia Foundation recommends prophylaxis for children
with severe hemophilia to reduce frequency of bleeding episodes. Usually,
such programs are initiated with the first joint hemorrhage.
Hepatitis B and A vaccination.
Avoid trauma, I.M. injections & aspirin.
2. During bleeding episodes/peri operative

a. Factor VIII replacement
1. IV infusion recombinant factor VIII dose is according to site & severity
Minor bleeding: the factor VIII level should be raised to 20–30 IU/dL.
Severe bleeding: the factor VIII should be raised to at least 50 IU/dL.
Major surgery: the factor VIII should be raised to 100 IU/dL
preoperatively and maintained above 50 IU/dL until healing occurred.
2. Others e.g.
Cryopreciptate
Fresh frozen plasma

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b. Ancillary therapy
a. Desmopressin
(D - amino- D - Arginine VasoPressin; DDAVP)
Role: Increases F VIII level by 4 folds
Alternative to recombinant F VIII in mild
bleeding in mild hemophelia
Intra nasal or Intravenous (0.3 P gm /kg in 50
ml saline over 20 min)
b. Antifibrinolytics
Role: inhibit fibrinolysis o stabilizes the clot
Indication: - Adjuvant therapy to recombinant factor VIII in mucosal
bleeding (oral bleeding, or epistaxis) due to high fibrinolysins in saliva
Avoided: - In urinary tract hemorrhages to avoid risk of intra renal clot
formation and obstructive uropathy
Examples: Epsilon Amino Caproic Acid (EACA),Tranexamic acid
c. Special situations e.g.
F VIII dose (IU/kg) Other lines
Intra cranial 50 IU/kg / 8 hours Urgent hospitalization
hemorrhage Then / 12 hours for 8 days
Then / 24 hours for 7 days
Epistaxis and 25 IU/kg / day EACA 50 mg/kg/6hrs
oral bleeding For 1 week
Hematuria and 25- 50 IU/kg / 12 hours Followed by prednisone
Hemarthrosis* for 1-3 days short course for 3-5 days
*Hemarthrosis care include rest, immobilization, cold compresses and elevation
Complications of hemophilia
A. Due to bleeding
- Hemophilic arthropathyojoint stiffness & Muscle atrophy
- Severe intracranial hemorrhage.
- Severe blood losso hypovolemic shock
B. Complications of transfusion (See chronic transfusion in thalassemia )
C. Complications of factor VIII therapy
1. Hypersensitivity reactions
2. Factor VIII inhibitors (Antibodies)
Develop in about 5-10 %
Hemorrhage become refractory to treatment
Inhibitors (measured by Bethesda Units) should be screened for annually

Page | 128
Treatment options
Low responders High dose factor VIII
(< 5 Bethesda Units)
High responders 1. Prothrombin complex concentrate (contain
( >10 Bethesda Units) prothrombin, F VII, F IX, F X)
2. Recombinant activated factor VII (NovoSeven)
3. Immune tolerance induction: daily infusion of
the missing protein till inhibitors disappears
4. Rituximab (Anti CD -20)
Other hemophilias
Hemophelia B (Christmas disease)
Factor IX deficiency.
Incidence: 1 / 50.000(in contrast to hemophelia A which is 1 / 10.000)
Sex-linked recessive disorder.
As hemophelia A but milder.
Treated by: Recombinant factor IX or factor IX concentrate given/24
hours.
Prophylactic treatment: Recombinant factor IX twice a week.
Hemophelia C
Factor XI deficiency.
Autosomal recessive disorder so can affect both sexes.
Very mild disease.
Treated by fresh frozen plasma given / 48 hours.

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Von Willebrand Disease; VWD (Vascular Hemophelia)
Von Willebrand factor ( VWF) is a large multimeric glycoprotein

Synthesized in megakaryocytes and endothelial cells
Stored in platelet and endothelial cell
Functions :VWF is essential for
- Platelet adhesion to sub endothelial matrix after vascular damage
- Carrier for F VIII protecting it from proteolysis
Deficiency
R VWF deficiency results in: Platelet dysfunction and decrease plasma F VIII.
R Pattern of deficiency: low(type 1) or abnormal (type 2) or absent (type 3).
R Inherited mainly as autosomal dominant disorder
R Diagnosed more in women than in men
R The commonest hereditary bleeding disorder , and some reports suggest that
it is present in 1-2% of the general population
Clinical picture
Mild bleeding: commonly mucocutaneous hemorrhage including skin
bruising, epistaxis, gum bleeding and menorrhagia.
May be post operative bleeding
Very rarely severe bleeding episodes or hemarthrosis (type 3)
Because VWF is an acute-phase protein, stress will increase its level. Thus,
patients may not bleed with procedures that incur major stress, such as
appendectomy and childbirth, but may bleed excessively at the time of
cosmetic or mucosal surgery (Nelson Textbook Of Pediatrics, 2016)
Investigations
A. Screening
Long bleeding time + long PTT + Normal PT
Normal results on screening tests do not preclude the diagnosis of VWD
B. Diagnostic
Note: if the history is suggestive of a mucocutaneous bleeding disorder, VWD
testing should be undertaken
Tests
1. Quantitative assay for VWF antigen
2. Testing for VWF activity (Ristocetin cofactor activity)
3. Determination of VWF structure (VWF multimers)
4. F VIII assay (F VIII decreases in some subtypes ;Type 2N vWD)
5. Platelet count And platelet adhesion test

Page | 130
Treatment
1. Minor bleeds require no treatment
2. Desmopressin is effective especially in type 1(mainstay of treatment)
3. Antifibrinolytics (e.g EACA) o as adjuvant treatment in oral bleeding.
4. VWF replacement therapy
Indications
For severe bleeding episodes.
The only effective treatment in type 3.
Use
Cryoprecipitate
Fresh frozen plasma.
Purified or recombinant VWF concentrates (containing no factor VIII)
may become available in the near future

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Disseminated Intravascular
Coagulation (DIC)

Wide spread activation of clotting factors all over the body resulting in:
Thrombosis and ischemia of different vessels.
Consumption of coagulation factors o bleeding.
Microangiopathic hemolytic anemia & thrombocytopenia.
Predisposing factors
Severe tissue damage e.g. in shock, dehydration, burn, hyperthermia,
crush injury,ashyxia.
Sepsis: meningeococcal, pneumococcal ,rickettsia, malaria, viral
Snake bites
Tumors e.g. AML, disseminated malignancy e.g. neuroblastoma
Incompatible blood Transfusion
Protein C deficiency; congenital or acquired with purpura fulminans
Gastro intestinal causes e.g. fulminant hepatitis, pancreatitis, severe
inflammatory bowel disease
Clinical picture
Manifestations of the cause.
Bleeding first occurs from sites of venipuncture, ecchymosis , purpura.
Thrombotic manifestations: gangrene in the skin, subcutaneous tissues,
extremities or renal infarction.
Severe anemia o Shock
May be multi organ system failure
Investigations(3C)
1. Investigations for the Cause
2. Coagulation profile:
Defective all phases of coagulation ; prolonged PT , aPTT, thrombin
time, and low fibrinogen.
Prolonged bleeding time
Fibrinogen degradation products (FDPs, D-dimers) appear in the blood.
The D-dimer assay is as sensitive as the FDP test and more specific for
activation of coagulation and fibrinolysis.
3. CBC/blood smear:
Anemia
Fragmented and burr- and helmet-shaped
red blood cells (schistocytes)
Thrombocytopenia

Page | 132
Treatment
The 1st 2 steps in the treatment of DIC are the most critical:
1. Aggressive treatment the trigger that caused DIC and

2. Restore normal homeostasis by correcting the shock (fluids/blood
transfusion), acidosis, and hypoxia that usually complicate DIC.
3. Control of bleeding
Platelet infusions for marked thrombocytopenia .
Cryoprecipitate for hypofibrinogenemia.
Fresh frozen plasma for replacement of other coagulation factors and
natural inhibitors.
4. Heparin use is controversial ; used only in:

Purpura fulminans
Chronic low grade DIC with giant heamangioma
Severe ischemic manifestations.
Prognosis
Generally bad , primarily dependent on the outcome of the treatment of the primary
disease and prevention of end-organ damage

Page | 133
Evaluation of a bleeding child

Is there an emergency?
* Does the patient need immediate resuscitation or senior help?
* Is the patient about to exsanguinate (shock, coma)?
* Is there hypovolemia (postural hypotension, oliguria)?
* Is there CNS bleeding (meningism, CNS, and retinal signs)?
* Is there an underlying condition that escalates this apparently minor bleeding
into an evolving catastrophe e.g .
- GIT bleeding in a jaundiced child (ie, coagulation factors already depleted)
- Bleeding in someone who is already anemic
History
Present history
Age of onset: early in hereditary coagulaopathy hemophilia
Site of bleeding: skin, mucosal or internal
Duration of bleeding
Outcome of bleeding
Relation to trauma or viral respiratory infection
Secondary cause eg drugs (warfarin), alcohol, liver disease, sepsis
Severity of bleeding: is it spontaneous or traumatic
Past history: Drugs/ operations / transfusions
Family history: For similar cases or consanguinity
Menstrual history: For adolescent girls
Examination
* Purpura
Multiple, spontaneous hemorrhages in the skin & mucous membranes.
Range from pin point (petechiae) to several centimeters (ecchymosis)
* Coagulopathy
Hematomas in deep structures e.g. muscle hematomas
Extensive ecchymosis
Hemarthrosis
Associations
Organ system failures
Other systems involvement
Underlying systemic disease
Workup
1. Complete blood count / blood film
2. For purpura (See before)
3. For coagulopathy: (See before)
4. For an etiology /association e.g. sepsis workup in DIC, renal function in HUS,....

Page | 134

Leukemia
Definition
Group of malignant diseases of hematopiotic cells in bone marrow
Giving rise to uncontrolled clonal proliferation of cells
With arrest of maturation at different stages
With subsequent marrow failure.
Risk factors
The etiology of ALL is unknown, although several genetic and environmental
factors are associated with childhood leukemia
1- Genetic predisposition
2- Chromosomal anomalies e.g. Down
3- Chromosomal breakage disorders e.g. Fanconi anemia, Bloom syndrome, ataxia
telangiectasia
4- Immunodeficiency states
5- Ionizing irradiation which either diagnostic irradiation or therapeutic
6- Chemical carcinogens: Benzene, Pesticide, Alkylating agents.
7- Viral infections
Classification
Acute leukemia Chronic leukemia

p
- Chronic myeloid leukemia
Acute lymphoblastic Acute myeloid (Philadelphia chromosome +ve)
leukemia leukemia - Chronic lymphocytic leukemia
(75%) (20%)
Acute undifferentiated
Leukemia
Acute mixed
lineage leukemia

Page | 135
Acute Lymphoblastic Leukemia (ALL)

Incidence
Peak age = 2-5 years, more in boys than in girls in all ages.
Among identical twins, the risk to the second twin if one develops leukemia is
greater than that in the general population
Classifications
1. Morphologic: (French – American – British) FAB classification.
L1 L2 L3
85 % 14 % 1%
Small cell Larger cell Large cell
Small cytoplasm Larger cytoplasm Vacuolated cytoplasm
Best prognosis Prominent nucleoli Worst prognosis.
Poor prognosis
2. Immunophenotyping
Classify ALL according to blast cell membrane & cytoplasmic markers.
1. Precursor B-cell ALL (CD10+ or common acute lymphoblastic leukemia
antigen [CALLA] positive)
The commonest ALL: 85 %
Best prognosis
2. T cell type
Less common : 15 %
Poor prognosis
3. B cell type(Burkitt type)
least common : < 1%
Worst prognosis
Clinical picture
I. The initial presentation of ALL
Usually is nonspecific and relatively brief.
Anorexia, fatigue, malaise, and irritability
Intermittent, low-grade fever.
Bone or, less often, joint pain, particularly in the lower extremities, may be
present
II. Manifestations of bone marrow failure
Anemia (erythriod cell infiltration, bleeding) o pallor
Thrombocytopenia o purpura , ecchymosis , orificial bleeding.
Granulocytopenia & granulocytic dysfunction o persistent infections
(bacterial, viral, fungal and protozoal) and persisting pyrexia

Page | 136
III. Manifestations of organ infiltration

Generalized lymphadenopathy
Hepatosplenomegaly (HSM)
Respiratory distress can occur in patients with an obstructive airway
problem (wheezing) due to a large anterior mediastinal mass (e.g., in the
thymus or nodes). This problem is most typically seen in adolescent boys
with T-cell ALL.
CNS leukemia: may manifest with:
- Raised intracranial tensiono headache, vomiting, coma or
- Focal lesion o fits, paresis, cranial nerve paralysis.
Testis o painless swelling
Kidneys o hematuria, renal failure
Bone swellings (infiltration) / Arthritisolimping
Investigations
A. For diagnosis
1. CBC/Blood smear
- WBCs: o Count may be normal, low or high.
o Blood smear show leukemic blast cells , but absence of blasts
doesn’t exclude leukemia.
- Platelets: oThrombocytopenia
- RBCs: o Normocytic anemia.
2. Bone Marrow examination

- Increased cellularity; marrow is replaced by 25% leukemic blasts cells ; all
are having malignant features
- Reduced erythroid and megakaryocytic cells
Blast cells must be subjected to:

1. Cytochemistry of blast cells show:
- Absent peroxidase positive granules
- Positive periodic acid schiff in clumps.
2. Immunophenotyping.
3. Cytogenetic studies
4. Immunoglobulin and T-cell receptor (TCR) gene re arrangement studies

Page | 137
B. To detect infilterations
Lumbar puncture is done during workup ;approximately 5-10% show
leukemic spread to the CSF
Brain MRI scan
Chest X-ray:
Mediastinal mass often present in T -ALL
Abdominal sonogram
Bone survey for bone infiltration.
C. For planning therapy
Biochemistry, serum uric acid, renal and liver biochemistry
Cardiac function; ECG and Echocardiogram
1. Infections
Disease Similarity to leukemia Exclusion from leukemia
Typhoid Prolonged unexplained fever Blood culture /Serology
Brucellosis Absent blast cells
Infectious Fever Absent blast cells
mononucleosis Organomegaly Monospot test
Purpura Positive IgM anti EBV
Perussis Fever No organomegaly
Leukemoid reaction (WBCs WBCs are mature lymphocytes
count > 50.000/mm3 ). Normal blood smear & BM
2. Hematologic /oncologic disorders
ITP BM Aplasia BM infiltration Hypersplenism
e.g. Neuroblastoma
Clinical Isolated Purpura Purpura Purpura
purpura in Pallor Pallor Pallor
clinically Pyrexia Pyrexia Pyrexia
well child No organomegaly Organomegaly Splenomegaly
(Abdominal mass)
Blood pPlatelets Pancytopenia Pancytopenia Pancytopenia
film
Bone Megakaryocyte Hypoplastic Infiltrated Hyperplastic
Marrow hyperplasia No blasts Abnormal cells No blasts
No blasts

Page | 138

4. Rheumatologic disease e.g.
Rheumatic fever/Juvenile rheumatoid arthritis/SLE
Cause fever and arthritis/limping
Other specific clinical features & Lab workup for lupus
Blood film and bone marrow exclude leukemia
5. Acute myeloid leukemia
Myeloblasts have: - Peroxidase +ve granules.
Positive PAS (diffuse reaction).
Immunophenotyping.
Cytogenetic studies
Prognosis
Prognostic factors
Clinical
Age
Sex
Leukemic burden
Response to therapy
Laboratory
Initial WBC count
Immunophenotyping
Cytogentics
Risk group Clinical features Molecular/genetic
features
Low risk Rapid response to induction therapy DNA index >1.6
Age 2-10 years Polypliody
WCC < 50 x 109/L t(12;21) or some
Precursor B cell phenotype trisomies
No central nervous disease
No testicular disease
C-ALL or L1
High risk Induction failure ; > 4weeks to Hypopliody
remission Presence of t(9;22)
Age > 10 years or t(4;11)
High minimal residual disease
N.B: The single most important prognostic factor in ALL is the response to treatment

Page | 139

Treatment of ALL
A. Supportive
1. Psychological & nutritional support
2. Control infections by
Education of patients, relatives and staff
about hand washing and isolation facilities
and mouth care
Anti-microbial protocols in case of fever
Granulocyte colony stimulating factor (G-CSF)
Or
Granulocyte Monocyte Colony Stimulating Factor (GM-CSF) for
granulocytopenia; < 500 cell /mm3

Prophylactic treatment for Pneumocystis jiroveci pneumonia
3. Control bleeding by: Platelet transfusion if < 10-20 .000 / mm3
4. Control anemia by: Packed red cells if hemoglobin falls below 7 gm/dl.
5. Avoid tumor lysis syndrome
x High-count ALL (especially T-cell) and B-cell NHL (specifically
Burkitt lymphoma) have the potential for bulky disease – a high cell
mass, which will undergo lysis with treatment, resulting in the
intracellular contents of potassium, phosphate and nuclear debris being
released into the circulation
x Lymphoblast cells have four times the amount of phosphate compared to
normal white cells
x Uric acid crystals and phosphate (precipitating out with calcium)
crystals may cause acute renal failure and the following:
Rise in urate
Within 1-2 days; rise in phosphate with concomitant hypocalcaemia
Then rapid development of hyperkalemia
Prevention
Treatment of hyperkalaemia
Hyperhydration: Intravenous fluids without added potassium
Alkalinaization prior to chemotherapy
Uric acid-lowering agents : Urate oxidase (Rasburicase) is the drug of
choice or Allopurinol
Dialysis or hemofiltration

Page | 140
B. Specific treatment
1. Induction of remission
Aim o Eradicate malignant cells in bone marrow (i.e. remission).
Duration o 4 weeks
Drugs Vincristine weekly (IV)
Prednisone daily (Oral)
L-asparaginase (IM)
CNS therapy ; see below.
Daunomycin at weekly intervals for patients at higher risk
Criteria of remission: With this approach, 98% of patients are in remission
* Clinical o No organomegaly nor detectable extramedullary disease
* CBC o No blast cells in peripheral blood nor in the CSF
* BM o Balst cells < 5%; none are having frank malignant features
2. CNS prophylaxis (CNS therapy)
Target Patients who, at the time of diagnosis, have lymphoblasts in the
patients CSF and either an elevated CSF leukocyte count or physical signs
of CNS leukemia, such as cranial nerve palsy.
Aim Prevent later CNS relapsesoThe likelihood of later CNS relapse
is reduced to <5%.
Duration o 4 weeks
Drugs Intrathecal methotrexate.
A small percentage of patients with features that predict a high
risk of CNS relapse may receive irradiation to the brain
3. Consolidation and intensification phase
Aim: Maintain remission and avoid relapse
Many regimens provide 14-28 wk of multiagent therapy
Drugs and schedules used vary depending on the risk group of the patient.
4. Maintenance phase of therapy
Aim oMaintain remission
Duration o Lasts for 2-3 yr, depending on the protocol used.
Drugs Oral 6 mercaptopurine daily .
Intravenous methotrexate weekly.
Usually with intermittent doses of vincristine and corticosteroid.

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C. Bone marrow transplantation

Done in the first remission for high-risk patients such as those with the t(9;22)
translocation known as the Philadelphia chromosome or extreme hypodiploidy
Complications
A. Complications of chemotherapy
- Bone marrow depression o Pancytopenia.
- Vincristine o Neuritis.
- Methotrexate o Renal toxicity.
- Adriamycin o Cardiomyopathy.
B. Relapse
Defined by any of the following
a- More than 25% lymphoblasts in bone marrow
or
b- Leukemic cell infiltration in the CNS or the testis.
Possible causes
- Persistence of leukemic cells in hidden sites (CNS, testis)
- Drug resistance
Decision
- Intensive chemotherapy and bone marrow transplantation
- Local irradiation
Minimal Residual Disease (MRD)

R Patients in clinical remission can have minimal residual disease (MRD) that
can only be detected with specific molecular probes to translocations and
other DNA markers contained in leukemic cells or specialized flow
cytometry.
R MRD can be quantitative and can provide an estimate of the burden of
leukemic cells present in the marrow.
R Higher levels of MRD present at the end of induction suggest a poorer
prognosis and higher risk of subsequent relapse.
R MRD of 0.01-0.1% on the marrow on day 29 of induction is a significant
risk factor for shorter event-free survival for all risk categories, when
compared with patients with no MRD

Page | 142

Acute Myeloid Leukemia (AML)
Other names: Acute Myeloblastic Leukemia, Acute non-lymphoblastic Leukemia
Risk factors
- Chromosomal anomalies e.g. Down, Fanconi anemia, Bloom syndrome.
- Anti neoplastic drugs.
FAB classification
M0 : Acute myeloblastic leukemia without differentiation
M1 : Acute myeloblastic leukemia with minimal maturation
M2 : Acute myeloblastic leukemia with maturation
M3 : Acute Pro myeloblastic leukemia
M4 : Acute Myelomonocytic leukemia
M5 : Acute Monocytic leukemia
M6 : Acute Erythroleukemia
M7 : Acute Megakaryocytic leukemia
Clinical picture
As ALL
Signs and symptoms that are uncommon in ALL, including
1. Subcutaneous nodules or “blueberry muffin” lesions (especially in infants)
2. Chloromas (discrete granulocytic masses):
Typically are associated with the M2 with a t(8;21) translocation.
Common sites : retro orbital (o proptosis),skin and epidural space.
3. Signs and laboratory findings of disseminated intravascular coagulation
(especially indicative of M3).
4. Infiltration of the gingiva (especially in M4 and M5 subtypes)
“Blueberry muffin” lesions Chloromas Gingival hypertrophy

Investigation:
As for ALL
Bone marrow show myeloblasts which have:
- Peroxidase positive granules.
- Positive PAS (diffuse reaction)
- Some have Auer Rods
Immunophenotyping and cytogenetic studies of blast cells

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Treatment
x Unlike ALL ; therapy for AML is
Of shorter duration
More intensive
Profound bone marrow aplasia ( except for M3 subtype) is usually
necessary.
Require more aggressive supportive care during the lengthy periods of
marrow suppression
Overall outlook is less optimistic with survival rates reported of 50-70%
x Induction chemotherapy includes
Commonly used regimens use cytarabine and an anthracycline
In combination with other agents such as etoposide and/or thioguanine
x Hematopoietic stem cell transplantation
The treatment of choice for:
High risk cases
Refractory cases
Relapsed case
Matched-sibling bone marrow or stem cell transplantation after remission
has been shown to achieve long-term disease-free survival in 60-70% of
patients
x Acute promyelocytic leukemia (FAB-M3)
Characterized by
A fusion gene involving the retinoic acid receptor t(15;17)
Very responsive to All-Trans-Retinoic Acid ; ATRA (Tretinoin)
combined with anthracyclines and cytarabine.
ATRA allows maturation of the accumulated promyelocytes
The success of this therapy makes marrow transplantation in first
remission unnecessary for patients with this disease.

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Lymphoma
Definition
Malignant tumors of lymph nodes (LN) and extra nodal lymphoid tissue.
1- Hodgkin disease(HD): Mainly nodal disease
2- Non Hodgkin lymphoma(NHL): Mainly extra nodal disease
Incidence: 13 : million children
Hodgkin Disease
B-lymphocyte malignancy.
With characteristic Reed-Sternberg cells.
Peak age o Bimodal; 15-30 and > 60 years ; rare before 5 years.
Histologic classification
Histologic type Incidence Criteria
1. Nodular sclerosing 50% Good prognosis
Females > males
Mediastinal mass common
2. Mixed cellularity 40% Present with more advanced disease
3. Lymphocyte 10% Best prognosis
predominance
4. Lymphocyte depletion Very rare Present with disseminated disease
type Poor prognosis
Clinical picture
1. Lymphadenopathy (Variable size)
Sites Criteria Effects

- Cervical (75 %) - Painless - Mediastinal syndrome: cough, dyspnea,
- Supraclavicular - Rubbery dysphagia, & facial edema
- Mediastinal - Discrete - Mesenteric: - Abdominal mass.
- Mesentric - Later become - May be intestinal obstruction
matted and fixed

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2. B Symptoms
Unexplained intermittent fever (Pel-Ebstein fever).
Night sweating requiring change of clothes.
Unexplained loss of body weight > 10% in the last 6 months.
3. Other rare constitutional symptoms and extra nodal involvement
Fatigue, pruritus, anorexia
Splenomegaly with or without hepatomegaly.
Bone marrow failure.
"Modified Ann – Arbor staging"
Based on radiograph and CT of chest, abdomen, and pelvis with or without bone
marrow biopsy.
I Confined to single lymph node region
II Involvement of two or more nodal areas on the same side of the
diaphragm
III Involvement of nodes on both sides of the diaphragm
IV Spread beyond the lymph nodes eg liver or bone marrow
Each stage is either
A : Absent of B symptoms
B : Presence of B symptoms
Investigations
A. For definitive diagnosis: Lymph node biopsy
B. For staging
Chest and abdominal CT scans is the investigation of choice for staging
Positron emission tomography (PET): Is increasingly being used for staging,
assessment of response and direction of therapy
C. Indicators of disease activity
ESR:is usually raised
Serum lactate dehydrogenase; raised level is adverse prognostic factor
D. Others
Chest X-raymay show mediastinal widening, with or without lung involvement
Liver biochemistryis often abnormal, with or without liver involvement.
Bone marrow aspirate and trephine biopsyseldom done but show
involvement in patients with advanced disease; this is unusual at initial
presentation (5%).

Page | 146
Management
Treatment is determined largely by disease stage, presence or absence of B
symptoms, and the presence of bulky nodal disease.
Generally; treatment involves combined chemotherapy with or without low-
dose involved-field radiation therapy
The combination chemotherapy regimens in current use are based on:
COPP (cyclophosphamide, vincristine [Oncovin], procarbazine, and
prednisone) Or ABVD (doxorubicin [Adriamycin], bleomycin,
vinblastine, and dacarbazine),
For intermediate- and high-risk ; with the addition of prednisone,
cyclophosphamide, and etoposide (ABVE-PC and BEACOPP) or
BAVD (brentuximab vedotin, doxorubicin [Adriamycin], vincristine,
dacarbazine) in various combinations
Novel promising agents that target RS tumor cells:
Anti- CD20 antibody (rituximab)
Anti-CD30 agents (Brentuximab)
Anti-CD30 antibody linked to the antimitotic agent monomethyl
auristatin E Brentuximab vedotin
Generated EBV-specific cytotoxic T lymphocytes (CTLs)

Page | 147
Non-Hodgkin Lymphoma
Incidence
- 3 times common than Hodgkin in children
- Peak age around 3 years
- ƃƂUDWLR
Aetiology
The cause is unknown.
Infective agents associated with development of NHL e.g. Ebstein Barr virus
(%XUNLWW¶VO\PSKRPD)
Diseases known to predispose to NHLs
Congenital immunodeficiency states.
Acquired immunodeficiency e.g. HIV infection
Autoimmune disorders
Familial cancer syndromes
WHO Classification
1. B cell lymphoma e.g.
%XUNLWW¶VO\PSKRPDOHXNDHPLD
Precursor B lymphoblastic lymphoma/leukaemia
2. T/NK cell lymphomas e.g.
Precursor T cell lymphoblastic leukaemia/lymphoma
Diffuse large B cell lymphoma
Anaplastic lymphoma
Clinical features
i- Abdominal lymphoma (35%)
- Mainly B cell type; start in payer¶s patches, and mesenteric lymph nodes.
- Presentation:
1- Rapidly enlarging abdominal mass with abdominal pain.
2- May be: - Ascites.
- Hepatosplenomegaly
- Intussusception.
ii- Anterior mediastinal mass: (25%)
- Mainly T. cell type; starts in thymus.
- Presentation:
1- Mediastinal syndrome (cough, dyspnea, dysphagia, face edema).
2- May be: - Pleural effusion.
- Pericardial effusion.
iii- Others
- Painless lymphadenopathy
- Bone marrow infiltrationo pancytopenia (occur in advanced lymphoma).
- CNS infiltration, oropharyngeal involvement, weight loss, bone pain,fever

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Investigations
1. Biopsy & immunophenotyping & cytogenitic studies.
2. Cytological examination of ascitic fluid, pleural fluid, B.M
3. Chest X-ray, CT scansof chest, abdomen and pelvis.
4. PET and gallium scans help in staging.
5. Bone marrow aspirate and trephine biopsyare always performed
6. Other investigations as Hodgkin disease
N.B: Burkitt’s lymphoma
Nature: B-cell type.

Histology: Starry sky appearance
Cytogenetics: May be (t 8; 14).
Types Endemic Sporadic

Distribution African World wide
Age Children Young adults
Site Jaw, Ovary Abdomen, Marrow
Association with Ebstein Barr virus In > 97%. In < 30%.
Treatment
1. Supportive; especially for life threatening complications:
Complication Action
1. Upper airway obstruction by - Corticosteriods
mediastinal mass - Local radiation
2. Tumor lysis syndrome - Rasburicase
- Superhydration.
- Na bicarbonate
2. Surgery: Only for small, easily, totally resectable tumors.
3. Chemotherapy:
Protocols combining chemotherapy, Local radiation & CNS prophylaxis
Protocols differ according to staging (localized or advanced) and
Immunophenotyping. It includes:
- High dose methotrexate (2-3 gm/m2) I.V along with folonic acid
- Rituximab
- Targeted irradiation with Rituximab as a carrier
- Allogeneic hematopoietic stem cell transplantation (HSCT)

Page | 149
Wilms' Tumor
(Nephroblastoma)
Embryonic tumor of the developing kidney
Very good overall prognosis – in excess of 90% 5-year survival rate
2nd common abdominal tumor
6% of malignancies in children around 3 years.
Age: usually occurs in children < 5 ys .
Types
1. Sporadic form (common): Usually unilateral.
2. Familial form: Usually bilateral.
3. Associations:
A. Congenital anomalies: in 15 %;
- Genito-urinary anomalies.
- Congenital aniridia .
- Hemihypertrophy e.g. Beckwith–Wiedemann syndrome.
B. Syndromes:
- WAGR syndrome : Wilms’, aniridia, genito-urinary anomalies,
retardation.
- Denys-Drash syndrome: Wilms’tumor, renal disease, genital anomalies
Clinical picture
Presents in a well child with a painless (or minimal discomfort) abdominal mass,
and/or haematuria and/or hypertension (independently or collectively)
1. Abdominal mass (the commonest presentation):
- Never cross midline (enlarged vertically)
- Usually unilateral; Bilateral in 5-10%
- Association: Microscopic hematuria.
2. Hypertension :
- In 60 % of cases
- Due to Renin-producing tumor or renal ischemia.
3. Others: - Polycythemia: occasional .
- Metastasis e.g. Lungs (commonest) o cannon-ball lesions.
Investigations
i. Detect the tumor:
1. Abdominal ultrasonography.
2. Abdominal CT: - Exclude neuroblastoma.
- Evaluate contralateral kidney.
- Evaluate metastasis
- CT guided biopsy.
3.Others: - Urine analysis for hematuria
- Renal functions tests

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Staging: Based on operative findings
Stage Tumor extent
I Limited to kidney & is completely excised
II Extends beyond the kidney but is completely excised
III Residual abdominal extension after surgery
IV Hematogenous spread to lungs, liver, bone,…
V Bilateral renal involvement at time of diagnosis
Differential diagnosis: Causes of abdominal mass
1. Neuroblastoma.
2. Hydronephrosis.
3. Renal cyst.
4. Others: Hypernephroma, Clear cell sarcoma
5. Mesoblastic nephroma
Treatment
1. Surgical: Radical nephrectomy
2. Chemotherapy
3. Radiotherapy

Page | 151
Neuroblastoma
Characters
Aggressive embryonal tumor of the autonomic system, originating from neural
crest-derived sympathetic nerve cells in the adrenal gland & sympathetic
ganglia (Abdomen // Thoracic // Cervical)
Most common cancer diagnosed at age <1 year
It accounts 8-10% of all childhood malignancies.
Has the biological potential to involute and resolve spontaneously or behave
aggressively with widespread metastases/organ invasion
Staging
Stage
I - The tumor is confined to site of origin.
II - The tumor extend beyond site of origin but not cross midline
III - Localized tumor with contralateral regional lymph node
involvement.
IV - Metastatic disease .
IVs - Stage I or II + involvement of skin, liver and/or BM .
Clinical picture
Presenting symptoms are extremely variable
1. Abdominal mass (commonest)
- Origin o adrenal medulla or abdominal sympathetic chain.
- Hard with irregular surface
- Located in upper quadrant of abdomen
- May cross midline as it enlarges horizontally
- May be ascitis , hepatomegaly
2. Mediastinal or cervical mass
* Origin: Thoracic or cervical sympathetic chain.
* Manifestations:
- Mediastinal syndrome: see before
- Horner syndrome (unilateral ptosis, enophthalmos, meiosis &
anhydrosis).
3. Spinal cord compression
* Origin o sympathetic chain.
* Manifestations: - Localized back pain
- Paraplegia.
- Sphincteric dysfunction.
4. Metastatic neuroblastoma
- BM o pancytopenia.
- Orbito Proptosis with ecchymotic eye lids o Raccoon like appearance.

Page | 152

5. Syndromes associated with Neuroblastoma
Eponym Features
Excessive catecholamine Intermittent attacks of sweating, palpitation, hypertension
, flushing, polyuria & polydipsia
Unilateral ptosis, myosis, and anhidrosis associated with a
Horner syndrome thoracic or cervical primary tumor.
Symptoms do not resolve with tumor resection.
Myoclonic jerking and random eye movement with or
without cerebellar ataxia.
Often associated with a biologically favorable and
Opsoclonus-myoclonus-
differentiated tumor.
ataxia syndrome
The condition is likely immune mediated, may not resolve
with tumor removal
Often exhibits progressive neuropsychological sequelae.
Intractable secretory diarrhea and hypokalemia due to
Kerner-Morrison
tumor secretion of vasointestinal peptides.
syndrome
Tumors are generally biologically favorable.
Diagnosis
1. Detect origin of 1ry site (adrenal, sympathetic chain)
- Abdominal ultrasonography & CT.
- Chest x ray & CT.
- Biopsy
2. Urinary catecholamines: Vallinyl mandelic acid & Homovanillic acid
Treatment
The usual treatment for low-risk neuroblastoma is surgery for stages 1 and 2 and
observation for stage 4S with cure rates generally >90%
Stage 3 : Surgery , radiotherapy and chemotherapy .
Stage 4 : Radiotherapy or chemotherapy
Therapies currently under investigation : radiolabeled targeted agents (e.g.
MIBG), monoclonal antibodies (anti–tumor-associated GD2) combined with
growth factors (GM-CSF), and antitumor vaccines

Page | 153
Lymphadenopathy
Causes
1. Nonspecific reactive hyperplasia
2. Infection
A. Bacterial: Staphylococcus, streptococcus, tuberculosis, atypical
mycobacteria, Bartonella henselae(cat scratch disease) brucellosis
B. Viral: Epstein–Barr virus, cytomegalovirus, rubella, rubeola
C. Protozoal: Toxoplasmosis, malaria
D. Spirochetal: Syphilis, rickettsia
E. Fungal: Histoplasmosis, cryptococcus, aspergillosis
3. Connective tissue disorders
A. Rheumatoid arthritis
B. Systemic lupus erythematosus
4. Hypersensitivity states e.g. Serum sickness
5. Lymphoproliferative disorders
6. Neoplastic diseases
A. Hodgkin and non-Hodgkin lymphomas
B. Leukemia
C. Metastatic disease from solid tumors: neuroblastoma, nasopharyngeal
carcinoma,
D. Histiocytosis
7. Storage diseases
A. Niemann–Pick disease
B. Gaucher disease
8. Immunodeficiency states
9. Miscellaneous causes
A. Kawasaki disease (mucocutaneous lymph node syndrome)
C. Sarcoidosis
E. Hyperthyroidism
Diagnosis
1. Thorough history of
- Infection
- Contact with rodents or cats
- Systemic complaints
2. Careful examination of the lymphadenopathy including
* All the lymph-node-bearing areas should be carefully examined
* Size, mobility, warmth, erythema, fluctuation & location.
To My mother and father

To My wife and kids
uploaded by: Dr.Maged
Almansour
Page | 154
* Texture of lymph nodes:

- Consistency: soft, firm, rubbery, hard
- Discrete or matted
- Tender (in inflammation or rapid malignancy) or not
3. Physical examination for
* Draining area in localized adenopathy e.g.
- Ear, nose and throat in cervical adenopathy
- Occipital adenopathy in infections of scalp
- Preauricular adenopathy in conjunctivitis and cat scratch disease
* Evidence of hematologic disease, such as hepatosplenomegaly and petechiae
4. Workup
* Blood count
* Erythrocyte sedimentation rate (ESR)
* Skin testing for tuberculosis
* Bacteriologic culture of regional lesions (e.g., throat)
* Specific serologic tests for e.g. Epstein–Barr virus (EBV)
* Chest radiograph ± CT scan
* Abdominal sonogram ± CT
* LN Ultrasonography
* Lymph node aspiration and culture
* Bone marrow examination if leukemia or lymphoma is suspected
* Lymph node biopsy
Indications
- Initial physical examination and history suggest malignancy
- Lymph node size is greater than 2.5 cm in absence of signs of infection
- Lymph node persists or enlarges
- Appropriate antibiotics fail to shrink node within 2 weeks
- Supraclavicular adenopathy.
Precautions
- Upper cervical and inguinal areas should be avoided
- The largest node should be biopsied, not the most accessible one.
- The node should be removed intact with the capsule, not piecemeal

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Class 14
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Splenomegaly
* Spleen may normally be felt in children up to 3 or 4 years of age

* At an older age, the spleen tip is generally not palpable below the costal margin
and a palpable spleen usually indicates splenic enlargement two to three times its
normal size.
Causes of splenomegaly
I. Infectious splenomegaly
A. Bacterial: acute and chronic systemic infection, subacute bacterial
endocarditis, typhoid fever,and miliary tuberculosis
B. Viral: infectious mononucleosis (Epstein–Barr virus), cytomegalovirus,
hepatitis viruses
C. Spirochetal: Syphilis
E. Protozoal: malaria, toxoplasmosis, leishmaniasis, schistosomiasis,
trypanosomiasis
F. Fungal infections
II. Hematologic disorders
A. Hemolytic anemias
B. Extramedullary hematopoiesis as in osteopetrosis and myelofibrosis
C. Myeloproliferative disorders (e.g., polycythemia vera)
III. Infiltrative splenomegaly
A. Nonmalignant
1. Langerhans cell histiocytosis
2. Storage diseases such as Gaucher disease, Niemann–Pick disease,
amyloidosis and sarcoidosis
B. Malignant
1. Leukemia
2. Lymphoma
IV. Congestive splenomegaly: portal hypertension
B. Connective tissue disorders e.g.,
Systemic lupus erythematosus
Rheumatoid arthritis
VI. Primary splenic disorders
A. Cysts
B. Benign tumors (e.g., hemangioma, lymphangioma)
C. Hemorrhage in spleen (e.g., subcapsular hematoma)

To My wife and kids
Class 14
3XOPRQRORJ\

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Acute Pharyngitis
It include acute tonsillitis, pharyngitis or tonsillopharyngitis
Causes
Viral or Bacterial (group A E hemolytic streptococci is the commonest.).
Red , congested throat

Inflamed tonsils with
Complaint white or yellow exudates
Fever, anorexia Enlarged tender lymph
and malaise nodes on the front of the
Sore throat neck
Dysphagia Associations
Conjunctivitis (Adeno
virus)
Minute vesicles and
ulcers (Coxachie virus)
Complications
As that of scarlet fever +
Mesenteric adenitis (o abdominal pain).
Treatment
* Symptomatic for fever.
* Specific: e.g. 10 days course of antibiotic (5 days for Zithromax)
Penicillin V
Amoxicillin
Cephalosporins
Zithromax
Clarithromycin
* Surgical:
A tonsillectomy, with or without adenoidectomy
Indications:
1. The most common indication for adenotonsillectomy is adenotonsillar
hypertrophy associated with obstructive sleep apnea
2. Recurrent tonsillitis defined as :
Seven or more documented infections in 1 year
Five per year for 2 years
Or three per year for 3 years
3. Recurrent peritonsillar abscess
4. Multiple antibiotic allergies.

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Otitis Externa
“Swimmer’s ear”
Cellulitis of the soft tissues of the external auditory canal
Risk factors : trauma ,humidity, heat, and moisture in the ear
Essentials to diagnosis
Edema and erythema of the external auditory canal with debris or thick,
purulent discharge.
Severe ear pain, worsened by manipulation of the pinna.
Periauricular and cervical lymphadenopathy may be present
Management
Pain control
Removal of debris from the canal
Topical antimicrobial therapy, Fluoroquinolone eardrops are the first-line
Avoidance of causative factors

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Acute Otitis Media ( AOM)

Risk factors
Eustachian tube obstruction by adenoids or edema in upper respiratory infection
Others:Impaired host immune defenses, bottle feeding, genetic susceptibility
Causes
1. Viral; AOM is a known complication of bronchiolitis
2. Bacterial: mainly H. influenza , pneumococci, moraxilla catarrhalis
Clinical picture
Fever
Earache (irritability , rubbing the ears in infants)
Otoscopic examination:
Drum is congested, bulging
Middle ear effusion
Drum may be perforated ± discharge.
Acute OM Severe acute OM Draining acute OM Resolving acute OM

Complications:
Mastioditis: tender swelling behind the ear
Chronic ear infection: draining ears for 14 days or more
Treatment
* Symptomatic for pain & fever: ibuprofen or acetaminophen
* Specific
Antibiotic or observation?
For infants younger than 6 monthsĺ antibiotics are always
recommended on the first visit, regardless of diagnostic certainty
For children \HDUVZLWKXQFRPSOLFDWHGRWLWLVPHGLDZLWKRXW
otorrheaĺ optional 48 hours of observation
Antibiotics
Amoxicillin-clavulanate enhanced strength ;ES (14:1 ratio of
amoxicillin: clavulanate), with amoxicillin dose 90 mg/kg/d for 10 days
Alternatives: Ceftriaxone (injections for 3 days), Cefdinir, or
Cefpodoxime ĺThen, according to culture and sensitivity
Surgical :Tympanocentesis & drainage ± Tympanostomy tubes
Patients with tympanostomy tubes with acute otorrhea ĺototopical
antibiotics (fluoroquinolone eardrops) are first-line therapy

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Acute Sinusitis
The maxillary and ethmoid sinuses are most commonly involved. These
sinuses are present at birth.
Major risk factors: Upper respiratory tract infections and immunodeficiency
Causes
As in otitis media
Mixed infections
Clinical picture
* Fever and headache
* Purulent or mucopurulent nasal discharge & post nansal discharge cough
* Others:
- Nasal obstruction
- Halitosis (fetid breath odor)
- Diminished smell
- Periorbital edema
Investigations
Culture and sensitivity of sinus aspirate
Trans illumination test opaque sinus
Plain X ray skull
CT skull
Treatment
Symptomatic for pain & fever (paracetamol)
Specific:
1. Antibiotics for a minimum of 10 days or 7 days after resolution of
symptoms:
High dose amoxicillin or amoxicillin/clavulanate
Alternatives
Ceftriaxone
Cefdinir , Cefpodoxime, Cefixime, Cefuroxime
Neither Zithromax nor Cotrimoxazole are recommended
2. Saline nasal washes or nasal sprays can help to liquefy secretions and act as
a mild vasoconstrictor
3. The use of decongestants, antihistamines, mucolytics, and intranasal
corticosteroids has not been adequately studied in children and is not
recommended for the treatment of acute uncomplicated bacterial sinusitis
Surgical = Sinuscopic sinus surgery for chronic cases

(Nelson Textbook of Pediatric)

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Stridor
Definition
Harsh, continuous inspiratory sound due to variable obstruction in upper airways
(larynx and trachea); may be associated with hoarseness of voice and respiratory
distress
Causes
Acute
Infectious Non infectious
* Viral:
Laryngeotracheobronchitis Laryngeal foreign body.
Acute laryngitis. Laryngeospasm(e.g. tetany).
Spasmodic laryngitis. Laryngeal edema(e.g. allergic)
* Bacterial: Laryngeal compression.
Acute epiglottitis.
Acute tracheitis (staph. aureus).
Diphteritic laryngitis.
Chronic
Congenital Acquired
Laryngeomalacia Laryngeal
Laryngeal web or cyst Stenosis
Tracheomalacia Tumors
Congenital vascular ring Paralysis
Tracheal stenosis
Severity of Stridor / Croup

Mild Moderate Severe
Stridor ± + ++
Sternal tug - + ++
Recession - + ++
Accessory - + ++
muscles
Nasal flare - + ++
Cyanosis - - +
Drooling - - +
Air entry Normal Reduced Poor
Hydration Normal Normal/reduced Reduced
If the child does not object:
Saturation Normal Normal/reduced Reduced
Heart rate Normal Raised Raised (bradycardia is
pre-terminal event)
(Oxford Paediatric Emergency Medicine)

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Acute Infectious Stridor

Laryngeotracheobronchitis (Croup)
Affects children 6 months - 6 years in the fall and early winter

Cause: Viral
Para-influenza types 1, 3
Others: RSV, influenza, adenovirus, corona virus
Presentation
Upper respiratory catarrh (Rhinitis, low grade fever)
Croupy ,barking, cough
Hoarseness of voice
Absence of drooling and toxic appearance
Croup severity:
Can be severe with inspiratory and expiratory stridor and respiratory
distress (substernal & suprasternal retractions)
Neck X ray
Steeple sign: Sub glottic narrowing in antero posterior view
Complication : Rarely; secondary bacterLDOLQIHFWLRQĺ%DFWHULDOWUDFKHLWLV
Acute laryngitis
Less severe croup (inspiratory stridor)
No respiratory distress
Spasmodic laryngitis
Viral but may be allergy or psychogenic (afebrile illness)
Occurs at midnight
Less severe
Recurrence is common
Acute epiglottitis and acute tracheitis : see later

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Management
Most cases respond to home treatment
Indication for hospitalization
Progressive stridor
Severe stridor at rest
Respiratory distress; hypoxia, cyanosis, depressed mental status
Poor oral intake
Mild croup (barking cough and no stridor at rest)
Oral hydration
Minimal handling
Mist therapy (no evidence to support its use)
Moderate to severe stridor at rest
1. Oxygen for patients with oxygen desaturation
2. Nebulized epinephrine
Racemic adrenaline nebulizer (0.25-0.5 ml in 3ml saline),
L- adernaline 5 ml 1:1000 solution is equally effective
Value
Reduce need for intubation for moderate to severe stridor at rest
3. Oral corticosteroids
Dexamethasone: 0.6 mg/kg Oral or intramuscular as one dose.
Lower dexamethasone dose (0.15 mg/kg) is equally effective
Inhaled budesonide (2–4 mg)
Value
Improves symptoms even in mild stridor
Reduce need for intubation for moderate to severe stridor at rest
Outcome
Symptoms resolve within 3 Repeat nebulized

hours of glucocorticoids and epinephrine is required
nebulized epinephrine Respiratory distress persists
Hospitalization
Discharge Close observation
Supportive care: secure airway,
± intubation for 2-3 days
(Nelson textbook of pediatrics)

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Page | 163
Acute Epiglottitis (Supraglottitis)

Infection of the epiglottis by Hemophilus influenza type B(in pre vaccine era)
Strept pyogenes, Strept pneumoniae, nontypeable H. influenzae, & Staph
aureus, represent a larger portion of pediatric cases of epiglottitis in vaccinated
children
Clinical picture
Peak age = 2-7 years (now commoner in adults with sore throat)
Toxic child with high fever
Drooling of saliva (severe dysphagia)
The child is severely exhausted :
Voice is muffled.
Stridor is mild.
Little or no cough
The child prefer upright posture and
neck is hyperextended in an attempt
to maintain the airway
Laryngeoscopic examination shows large
“cherry red” swollen epiglottis but this
procedure and any minor procedure may
precipitate complete airway obstruction.
Management
Medical emergency, once suspected, the patient must be admitted to the PICU
Secure the Airway before any maneuver:
Endotracheal tube (or less often tracheostomy) is
indicated ,regardless degree of respiratory distress ,
placed either in an operating room or ICU
The artificial airway is kept in place for 2-3 days
O2 inhalation as needed
Blood culture and, if possible, epiglottic surface culture should be done.
Antibiotics:
Start parenteral Ceftriaxone or Cefotaxime or
Meropenem pending result of culture & sensitivity
Continue antibiotics for at least 10 days.
Lateral X-ray of the neck if done (after securing airway)
may show swollen epiglottis (Thumb sign)
N.B: Household contacts < 4 years with incomplete HiB immunization or
immunocompromised require Rifampin prophylaxis (20 mg/kg orally once a day maximum
dose 600 mg for 4 days) (Nelson textbook of pediatrics)

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Page | 164
Bacterial Tracheitis
Acute bacterial infection of the upper airway that is potentially life
threatening.
Staphylococcus aureus is the commonest cause
Often follows viral laryngotracheobronchitis
Commoner than acute epiglottitis basically because of introduction of Hib
vaccine in most vaccinations protocols ¥¥
Clinical picture
The early clinical picture is similar to that of viral croup
Instead of gradual improvement, patients develop higher fever, toxicity,
and progressive or intermittent severe upper airway obstruction that is
unresponsive to standard croup therapy
Differentiated from epiglottitis by:
1. Preceded by viral prodrome
2. No posture preference; the patient can lie flat
3. No dysphagia or drooling!!
4. Lateral neck radiographs show a normal epiglottis but severe
subglottic narrowing; irregular tracheal border (absent thumb sign)
5. During endotracheal intubation/ Bronchoscopy: Normal epiglottis and
the presence of deep red mucosa and copious purulent tracheal
secretions below the cords confirm the diagnosis
6. Although cultures of the tracheal secretions are frequently positive,
blood cultures are almost always negative
7. Despite the severity of this illness, the reported mortality rate is very
low if it is recognized and treated promptly
Treatment
Patients with suspected bacterial tracheitis will require
Direct visualization of the airway in a controlled environment
Debridement of the airway
Most patients will be intubated because the incidence of respiratory
arrest or progressive respiratory failure and respiratory arrest is high
Thick secretions persist for several days, usually resulting in longer
periods of intubation for bacterial tracheitis than for epiglottitis or
croup
Antistaphylococcal agents: vancomycin or naficillin or oxacillin
Supportive care in ICU including supplemental oxygen ,suctioning

To My wife and kids
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P a g e | 165 Illustrated Baby Nelson

Lower Respiratory Diseases
Chest Examination
Pneumonia Bronchopneumonia Pleural effusion Pneumothorax Hydropneumothorax Collapse

Inspection
- Movement Decreased Decreased bilateral Decreased Decreased
- Shape Normal Normal Bulge Retraction
Palpation
- Tracheal shift Central Central Shifted to opposite side To same
side
- Tactile vocal fremitus Increased ? Normal Decreased Decreased
Percussion
- Note Impaired note ? Impaired note Stonydull Hyperresonance Shifting dullness Dull
- Topography Lobar Bilateral Rising to axilla Allover the side Transverse upper border Lobar
Auscultation
- Breath sounds Diminished ? Normal vesicular Markedly diminished vesicular
bronchial
- Adventitious sounds Crepitations Bilateral wheezes ,
Crepitations
- Vocal resonance Increased May be normal Decreased
Bronchophony
Special signs -- -- Aegophony Coin test Succussion splash --

Page | 166
Pneumonia
x Pneumonia is an infection of the lower respiratory tract that involves the
airways and parenchyma with consolidation of the alveolar spaces
x Pneumonitis is a general term for lung inflammation that may or may not be
associated with consolidation
Anatomic classification
Lobar pneumonia: pneumonia of one or more lobes
Bronchopneumonia: scattered bilateral inflammation both lungs
Interstitial pneumonia: bilateral perihilar pulmonary inflammation
Etiologic classification
Category Etiologic agents
Bacterial Gram-positive: e.g. Strept Pneumonae, group B and A
streptococci ,Staphylococcus aureus
Gram-negative: e.g. H.influenzae , Legionella, Klebseilla
Viral Respiratory syncytial virus (RSV) parainflenza , influenza ,
adenovirus, Human metapneumovirus, Corona virus
Atypical Mycoplasma pneumoniae , Chlamydophila pneumoniae
Chlamydia trachomatis (in infants)
Mycobacterial Tuberculosis and atypical mycobacteria
Aspiration Oral anaerobic flora, with or without aerobes
Allergic Esinophilic pneumonia (Loffler’s syndrome)
Rickettsial Coxiella Burnetii
Opportunistics in Fungal e.g. Aspergillus , histoplasma , cryptococcus, candida
immunocompromised Protozoal ; Pneumocystis jiroveci (carinii)
Bacterila; Klebsiella, and proteus
Symptoms
Onset is variable from acute, sub-acute or gradual
General Fever, malaise , toxemia (worst in bronchopneumonia)
May be abdominal pain: Referred from lower lobe
pneumonia
Chest Cough (dry then productive)
Dyspnea and grunting
Signs
Respiratory distress
Tachypnea is the most consistent clinical manifestation of pneumonia,
nasal flaring, retractions and grunting
Cyanosis and lethargy in severe infection specially in infants

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Page | 167
Chest examination
Pneumonia ( See table previous page for pneumonia ± effusion)
Bronchopneumonia ( See table previous page)
Interstitial pneumonia:o Minimal chest findings.
o Prolonged expiration & wheezes are common
Viral or bacterial pneumonia?
1. Clinical
Large pleural effusion, lobar consolidation, and a high fever at the onset of
the illness are suggestive of a bacterial etiology
2. Investigations : See later
Investigations
A. Radiological
1. Chest X-ray findings:
A. Lobar pneumonia
Homogenous opacity in one or more lobes
With clear costopherinic angle (differentiate it from effusion)
Usually bacterial
Right sided middle lobe Left sided lower lobe Right sided upper lobe
pneumonia pneumonia pneumonia
B. Bronchopneumonia
Scattered opacities in both lungs
Viral or bacterial
C. Interstitial pneumonia
Scattered bilateral interstitial infiltrates and peribronchial cuffing
Hyperinflation, and atelectasis
Seen in viral bronchopneumonia and atypical pneumonia

Page | 168
D. Complications
Effusion, abscess, or pneumatoceles (single or multiple, thin-walled,
air-filled, cystlike cavities) may indicate S. aureus, gram-negative, or
complicated pneumococcal pneumonia.
Effusion (Left) Lung abscess (Right) Pneumatoceles (Right)
Meningitis, suppurative arthritis, and osteomyelitis are rare complications

of hematologic spread of pneumococcal or H. influenzae type b infection
2. Ultrasonography:
Highly sensitive and specific in diagnosing
pneumonia by determining lung
consolidations and air bronchograms or
effusions
Differentiate simple effusion and empyema
Guide thoracentesis of a loculated effusion
3. Contrast CT scan, CT or ultrasonography guided lung biopsy:
Reserved for complicated cases/ rare pneumonias
B. Laboratory
1- WBC count
In viral pneumonia usually not higher than 20,000/mm3, with a
lymphocyte predominance
In bacterial pneumonia, in the range of 15,000-40,000/mm3, and a
predominance of granulocytes
Mild eosinophilia is characteristic of infant C. trachomatis pneumonia
2- Acute phase reactants: High ESR, positive C-reactive protein and
Procalcitonin usually suggest bacterial rather than viral pneumonia
3- Isolation of an organism
Indicated for
Ill cases that require hospitalization
Immunocompromised patients
Patients with recurrent pneumonia
Pneumonia unresponsive to empirical therapy

Page | 169
Workup
Blood cultures are positive in 10% to 20% of bacterial pneumonia
Pleural fluid culture
Lung tracheobronchial secretions culture
Invasive: Bronchoscopy with bronchoalveolar lavage ,brush
mucosal biopsy, needle aspiration of the lung, and open lung biopsy
Specific testing e.g.
M. tuberculosis : tuberculin skin test, serum interferon-gamma
release assay, or analysis of sputum or gastric aspirates by
culture, antigen detection, or PCR
Detect the virus or viral antigens by DNA or RNA tests
4- Serology: for rising antibody titers:
- Cold agglutinins in 50% of mycoplasma pneumonia (non specific test).
- ASO titer in streptococcal pneumonia
Complications
Respiratory Systemic
Pleural effusion Meningismus especially with right
Empyema with or without upper lobe pneumococcal pneumonia
bronchopleural fistula and Heart failure
pyopneumothorax Distant infections e.g. Septicemia,
Lung abscess meningitis, pericarditis
Pneumatoceles Paralytic ileus
Unresolved pneumonia
These complications are more common
with Staph and Klebseilla pneumonia
Differential Diagnosis of pneumonia

1. Viral pneumonia
The commonest cause in pre-school children with peak at 2- 3 years
Causes: RSV, parainfluenza (1, 2, and 3) viruses, influenza (A and B)
viruses, human metapneumovirus, and adenovirus
Clinically: - Preceding upper respiratory tract infection for several days.
- Fever & respiratory distress milder than bacterial pneumonia.
- May be widespread wheezes and crepitations.
Diagnosis
CXR: Bilateral peri hilar infiltrates (bronchopneumonia or interstitial
pneumonia) ± Hyperinflation.
Pleural effusions, pneumatoceles, abscesses, lobar consolidation, and
“round” pneumonias are generally inconsistent with viral disease
CBC : normal or mildly elevated WBCs with predominant lymphocytes
Detect the virus or viral antigens by DNA or RNA tests

P a g e | 170 Illustrated Baby Nelson
2. Bacterial pneumonia
Pneumococcal* Streptococcal Staphylococcal H. Influenzae* Klebsiella
Age Commonest bacterial. Peak age 3-5 yr. Peak age below 1 year Peak age below 3 more in immune
pneumonia in History : staph skin yr deficient
children infection - Has high mortality
C/P - Moderate - Severe with extreme - Severe - Insidious onset - Severe , fulminant
- Moderate fever prostration - High fever - Prolonged - High fever with
- Usually lobar - High fever - May be course over copious purulent
- Bronchopneumia is - Bronchopneumonia bronchopneumonia weeks secretions
commoner in young with large pleural or lobar or hemithorax - Usually lobar; - Usually lobar
infants effusion - Complications involving two - Complications as
(abscess, empyema , or more lobes Staph.
pneumatoceles, and
pneumothorax)
* High incidence of penicillin resistance so treat with high doses of amoxicillin (80-90 mg/kg/24 hr) or cefuroxime or 3rd generation cephalosporin
3. Mycoplasma pneumonia (Primary Atypical Pneumonia): Common in school age (5-15 yr)
Clinically
Severe nonproductive cough without significant respiratory distress
Pharyngitis is common
Minimal physical signs (walking pneumonia)
May be chest wheezes and inspiratory crepitations
Diagnosis is mainly clinical.
Blood: CBC is usually normal, Cold agglutinins may be detected
Chest X-ray show:
Scattered bilarteral perihilar pulmonary infiltrates
Rarely: Lobar pneumonia ± effusion.
Page | 171
Treatment of pneumonia
i. Supportive
Bed rest, humidified O2 inhalation ± restricted I.V. fluids
Symptomatic treatment e.g. antipyretics for fever
Treatment of complications e.g. Heart failure.
Aspiration /drainage for effusion or empyema
Oral zinc (10- 20 mg/day) is recommended add-on in developing countries
ii. Specific treatment
1. Suspected bacterial pneumonia: Antibiotics
As suggested by clinical picture & chest X-ray
Based on the presumptive cause and the age
Antibiotic combination if the cause cannot be detected
Duration: For 10-14 days, 5 days if azithromycin is used
Empirical therapy
Milder cases Amoxicillin (50–90 mg/kg/dose) or Cefuroxime
or Amoxicillin clavulanate
Hospitalized cases
Children less than 4 weeks IV Ampicillin and an Aminoglycoside
Infants 4–12 weeks of age IV Ampicillin for 7–10 days
Older child fully immunized Yes ĺAmpicillin or penicillin G.
against H. influenzae type B No ĺParenteral cefotaxime or ceftriaxone
and S. pneumoniae
Suspected Staph Add vancomycin or clindamycin
Suspected Klebsiella Add aminoglycoside
Mycoplasma pneumonia Erythromycin or azithromycin or clarithromycin
In adolescents Fluoroquinolones may be considered
(Nelson textbook of Pediatrics, 2016)
2. Viral pneumonia
Antibiotics may be considered as a coexisting bacterial infection exists
in 30% of cases
An appropriate antiviral (e.g. Amantadine, Rimantidine, Osetamivir,
Zanamivir) should be considered for the child with pneumonia due to
Influenza
Prognosis
Uncomplicated community-acquired bacterial pneumonia show
improvement in clinical symptoms within 48-96 hr of initiation of
antibiotics.
Radiographic evidence of improvement lags behind clinical improvement.
Causes of none improvement with appropriate antibiotic therapy:

Page | 172
Complications, such as empyema

Obstruction from endobronchial lesions or foreign body
Bacterial resistance
Pre-existing Diseases: as causes of recurrent pneumonia***
Nonbacterial Etiologies such as viruses and aspiration
Recurrent pneumonia
Defined as 2 or more episodes in a single year or 3 or more episodes
ever, with radiographic clearing between occurrences
Underlying disorder
1. Hereditary disorders
Cystic fibrosis
Sickle cell disease
2. Immunodeficiency: Primary or secondary
3. Disorders of Cilia
Immotile cilia syndrome
Kartagener syndrome
4. Anatomic disorders
Aspiration (oropharyngeal incoordination)
Gastroesophageal reflux
Tracheoesophageal fistula (H type)
Foreign body
Bronchiectasis
Pulmonary sequestration
Lobar emphysema

Page | 173
Acute Bronchiolitis
Acute inflammation of the bronchioles
Usually viral infection
Respiratory syncytial virus (RSV) in 50% of cases
Others: human metapneumovirus, Adenovirus, Para influenza and
Mycoplasma
Incidence
Age: The 1st 2 years of life (peak age ~ 6 months)
Season: more in winter and spring
More in boys who are not breast fed
Pathogenesis
Viral invasion of small bronchioles mucosa & submucosa invaded
o acute inflammation o bronchiolar obstruction by edema, mucus
and cellular debris
Impaired pulmonary gas exchange ( hypoxemia , hypercapnia) may
occur with severe disease
Clinical picture
Symptoms
Mild upper respiratory catarrh (rhinitis , mild fever) for few days then
Gradually occurring dyspnea, cough and wheezy chest
Along with irritability, difficult feeding, air hunger
Apnea may be more prominent in very young infants (<2 mo old) or
former premature infants
Signs
1. Respiratory distress
Tachypnea, retractions, grunting ± cyanosis
Degree of tachypnea does not always correlate with the degree of
hypoxemia or hypercarbia, so pulse oximetry and noninvasive
determination of carbon dioxide are essential
2. Hyperinflation o Ptosed liver and spleen
3. Chest examination:
Inspection o Hyperinflated chest , prolonged expiration
Palpation o May be palpable wheezes and decreased TVF
Percussion o Bilateral hyper resonance
Auscultation o Diminished vesicular breath sounds.
o Prolonged expiration.
o Bilateral expiratory wheezes
o Bilateral fine crackles

Page | 174
Complications
Dehydration o due to tachypnea & anorexia
Lung collapse or pneumothorax o sudden deterioration
Respiratory failure
Heart failure
Investigations: Diagnosis of acute bronchiolitis is mainly clinical
Chest X-ray
R Indicated only for severe illness or bacterial superinfection suspected
R Shows:
Hyperinflation (horizontal ribs , flat diaphragm)
Bilateral perihilar infiltrates ± areas of atelectasis
Blood tests:
R ESR, CRP and white blood cell count o are usually normal
R Arterial blood gases for severe disease
Detect the virus by cell culture or viral antigen /RNA by PCR using
nasopharyngeal aspirate
Differential diagnosis: From other causes of wheezy infants e.g.:
x Bronchial asthma: suggested by
Recurrent attacks of wheezy chest ± viral prodrome
Related to certain allergens or exercise
Respond to anti-asthma therapy(bronchodilator trial)
Relatives with atopy or asthma/presence of atopy or dermatitis
x Congestive heart failure
x Aspiration syndromes /Foreign body inhalation.
x Cystic fibrosis
x Infections e.g. Pulmonary TB, Pertussis
Treatment
Treat at home or hospital?
Hospitalize if risk factors for severe disease exist e.g.
Infants younger than 3 months
Severe respiratory distress or apnea, oral feedings intolerance
Preterm birth
Underlying comorbidity

Page | 175
The mainstay of treatment is:

“Supportive care”
Nurse sitting with head and chest elevated at a 30-degree angle with
neck extended
Humidified cool oxygen inhalation with high-flow nasal cannula
Frequent suctioning of nasal and oral secretions often provides relief
of distress
Care of feeding ( more calories are required)
Parenteral fluids if risk of aspiration exists with respiratory distress
Treat complications e.g.
R Antibiotic therapy if secondary bacterial pneumonia suspected
R CPAP or intubation and mechanical ventilation if deterioration
with exhaustion or persistent apnea
Non evidence based and controversial strategies
1. Inhaled bronchodilator* Don’t modify disease course
2. Steroids* Don’t modify disease course
Prolong virus shedding
3. Combined nebulized epinephrine* & Under ongoing studies
oral dexamethasone Short term relief in severe cases
4. Nebulized hypertonic saline
5. Heliox
6. Chest physiotherapy
Should be avoided
7. Cough sedatives
* Frequently used
Home oxygen therapy
Low risk cases that require oxygen can be discharged ER on home oxygen
Criteria for home oxygen therapy includes
1. Mild illness as evident by feeding well ,alert and active; minimal
retractions; respiratory rate <50 breaths/min, no apnea
2. Age: 2 mo-2 yr of age with first episode of wheezing during RSV
season
3. Reliable family: good access to healthcare, can manage
secretions by bulb suctioning
4. Absent:
Toxic appearance or proven bacterial disease
Comorbidities: Cardiac, pulmonary, immunodeficiency, or
neuromuscular
(Nelson textbook of Pediatrics )

Page | 176
Antiviral
Ribavirin aerosol
Indications: risky infants (see later)
Side effect: controversial benefits and very costly
Prevention
Meticulous hand hygiene is the best measure to prevent nosocomial
transmission.
Monoclonal antibody to RSV F protein (Palivizumab) I.M is given before
and during RSV season for risky infants < 2 yr of age with:
Chronic lung disease
Gestational age is less than 35 weeks
Comorbidities e.g. congenital heart disease, immunodeficiency,
neuromuscular disorders
Prognosis
The median duration of symptoms is approximately 14 days; the first 2-3
days are the most critical
Mortality rate | 1% due to: apnea , respiratory failure, dehydration
There is higher incidence of wheezing and asthma in children with a
history of bronchiolitis

Page | 177
Bronchial Asthma
Definition
Asthma is a chronic inflammatory condition of the lung airways resulting in
airways hyper responsive to various stimuli and episodic airflow obstruction
with high degree of reversibility
Incidence
Boys/ girls: 2:1 before puberty and 1:1 after puberty.
Most asthmatic children become symptomatic before 5th year
Risk factors/associations
Parental asthma
Other allergies e.g. eczema, allergic rhinitis, food allergies
Rhinitis, sinusitis & gastro esophageal reflux disease (GERD).
Early weaning from breast milk before 4 months.
Pathogenesis
Genetic predisposition
Imbalance between T Helper 1 lymphocytes (Th1) & and T Helper 2 (Th2) with
raised Th2 o excessive release of proinflamatory cytokines (IL4, IL5, IL13)
Exposure to asthma triggers
- Accumulation of IgE in airways and blood (Type 1 hypersensitivity; atopy)

- Increased activated mast cells, eosinophils and chronic inflammatory cells in
airways
Bronchoconstriction and airways inflammation with edema, nmucus, nchronic

inflammatory cells
Airways narrowing especially in expiration

Persistent airway inflammation leads to
- Collagen deposition beneath basement membrane.

- Hypertrophy of muscles & glands.
Airway remodeling and persistent narrowing (Chronic obstructive airway

disease (Cor Pulmonale)
Asthma triggers includes
Respiratory viral infections
Animals with fur, dust mites, cockroaches
Aerosol chemicals
Changes in temperature e.g. early morning
Drugs (aspirin, beta blockers)

Page | 178
Exercise (? Air drafts moving in and out)

Pollens
Smoke, tobacco smoke
Strong emotional expression
Clinical picture
Asthma is strongly suggested with
1. History of any of the following:
Cough, worse particularly at night
Recurrent wheeze, difficult breathing or chest tightness
2. Symptoms occur or worsen
At night, awakening the patient
In a seasonal pattern
In the presence of a trigger
3. Symptoms respond to short-DFWLQJLQKDOHGȕ-agonist
4. History of other allergies eczema, hay fever,…
5. History of asthma or atopy in other family member
6. History of Patient’s colds often “go to the chest” or take longer to clear up
During an attack (Exacerbation)
Irritability, restlessness.
Respiratory distress (tachypnea, retractions…)
Chest signs
Chest wheezing (a normal chest examination does not exclude asthma)
Inspection o +\SHULQIODWHGFKHVWSURORQJHGH[SLUDWLRQDQGĻPRYHPHQW
Intercostals and subcostal retractions
Palpation o Decreased TVF and may be palpable wheezes
Percussion o %LODWHUDOK\SHUUHVRQDQFHZLWKĻKHSDWLF FDUGLDFGXOOQHVV
Auscultation o Diminished vesicular breath sounds with prolonged
expiration
o Bilateral expiratory wheezes
Types of asthma
1. Transient non atopic wheezing
Triggered by common respiratory viral infections
Usually resolves during childhood
2. Persistent atopy-associated asthma
Associated with atopy
Clinical e.g., atopic dermatitis in infancy, allergic rhinitis, food allergy
Allergen sensitization, Ĺ,J(DQGEORRGHRVLQRSKLOV
Tend to persist into later childhood with lung function abnormalities

Page | 179
Workups in asthma
“Diagnosis of bronchial asthma is mainly clinical”
1. Lung function tests
Usually feasible in children > 5 yr of age
A. Spirometry (in clinic)
FEV1 Forced expiratory volume in the 1st second
FEV1:FVC ratio Forced expiratory volume in the 1st second/ Forced
vital capacity
Findings in asthma
Low (relative to percentage of predicted norms or previous best)
Improve after inhaled bronchodilator
Worsen after exercise challenge
Spirometry is recommended at
least annually and more often if
asthma is poorly controlled or
abnormal lung functions detected
B. Peak Expiratory Flow (PEF)

Used for home monitoring
Less sensitive than spirometry
2. Immunologic
High IgE and eosinophils in the blood and sputum
Allergen sensitization : Skin testing with suspected allergens
3. Chest X-ray (During exacerbation) may show
Hyperinflation.
May detect complications e.g. collapse, pneumothorax

Page | 180
Treatment
Medications used in bronchial asthma
Reliever medicines
1. 6KRUWDFWLQJȕ$JRQLVWV 6$%$
Preparations Salbutamol
Albuterol
Levalbuterol
Action Selective E2 agonists; induce quick and short lived
bronchodilatation
Duration Short acting ; 4- 6hrs
Indication Drugs of choice for acute asthma symptoms (“rescue”
medication) and for preventing exercise-induced
bronchospasm
(2.5 – 5 mg by inhalation; dilute with saline to 3 mL)
Side effects Tachycardia and tremors (less with Levalbuterol)
Hypokalemia
Overuse of SABAs as a “quick fix” for asthma, rather
than using controller medications is associated with an
increased risk of death from asthma
2. Ipratropium bromide
Parasympatholytic
Used primarily as add on to SABA in treatment of acute severe asthma
125 – 250 microgram by inhalation; dilute with saline to 3 mL
Useful in wheezing due to bronchmalacia
Side effects : Mild atropine like / less potent than the ȕ-agonists
Controller medicines
1. Steroids
a. Inhaled corticosteroids (ICS)
Preparations Beclomethasone (Qvar)
Budesonide (Pulmicort)
Fluticasone (Flixotide)
Ciclesonide (Alvesco)
Action Potent anti-inflammatoryĺ reduce airway chronic
inflammation and remodeling
ĹĹ expression of E-receptors in bronchial muscles
Indication First-line treatment for persistent asthma
Available in metered-dose inhalers (MDIs), dry
powder inhalers (DPIs), or suspension for nebulization

Page | 181
Side effects a. Oral candidiasis (thrush)

b. Dysphonia (hoarse voice) due to vocal cord myopathy
Both are minimized by:
Using a spacer with MDI( reduce oropharyngeal
deposition of the drug)
Mouth rinsing after ICS use
c. ? Steroids systemic effects with high dose, long term ICS
b. Systemic corticosteriods
Preparations Oral: Prednisolone
Parenteral: Methyleprednisolone, Hydrocortisone
Indication Short courses to treat asthma exacerbations
Rarely, long courses in patients with severe disease
who remain symptomatic despite optimal treatment
Precaution Children who require routine or frequent short courses
of oral corticosteroids, especially with concurrent high-
dose ICSs, should receive corticosteroid adverse
effects screening and osteoporosis preventive
measures
2. Long Acting E2 Agonists (LABA)
Preparations
ĺ ¥
Action E
Indication
Precaution
Risks

3. Leukotriene receptor antagonist (LTRAs)

Preparations Montelukast (Singulaire); chewable tablets or sachets,
licensed above 6 months
Zafirlukast, licensed above 5 years

Page | 182
Action Leukotriene receptor antagonist with anti-

inflammatory and a bronchodilator effect
Indication Alternative treatment for mild persistent asthma
Add-on medication with ICS for moderate persistent
asthma
Reduce exercise-, aspirin-, and allergen-induced
bronchoconstriction.
Precaution Less effective than ICSs in patients with mild
persistent asthma
Risks Montelukast has rarely been associated with mood
changes and suicidality
4. Theophylline
Action 3KRVSKRGLHVWHUDVH LQKLELWRU ĺ EURQFKRGLODWDWLRQ DQG
anti-inflammatory
Use Alternative monotherapy controller agent for older
children and adults with mild persistent asthma
It is no longer considered a first-line agent for young
children
Precaution Narrow therapeutic window; therefore, when it is used,
serum theophylline levels need to be routinely
monitored
Overdose Headaches, vomiting, cardiac arrhythmias, seizures,
and death
5. Sodium cromoglycate
Mast cell stabilizer
Inhibit exercise-induced bronchospasm, they can be used in place of
SABAs, especially in children who develop unwanted adverse effects
with ȕ-agonist therapy (tremor and elevated heart rate).
Not a preferred controller ; must be administered frequently (2-4
times/day) and are not nearly as effective daily controller medications
Asthma medicines delivery systems
Metered dose inhaler with Dry powder inhaler with Solution for nebulization
a spacer metered dose turbohaler

Page | 183
Management of acute asthma exacerbation

A. At Home
Inhaled SABA (Salbutamol): 2.5 - 5 mg with saline by nebulizer up to
3 treatments in 1 hr OR
2-6 puffs SABA by MDI (puff=100 mcg) up to 3 treatments in 1 hr
Resolution of symptoms Incomplete response to initial treatment

No symptoms over the next 4 hr Persistent PEF < 80% of personal best
,PSURYHG3()RISHUVRQDOEHVW Deterioration
Continue SABA at 3-4 hr intervals

for 1-2 days Seek urgent medical advice
Contact your physician for advice
B. Emergency department treatment

Assessment of severity
Mild Moderate Severe
Altered consciousness Absent Agitated, confused
Cyanosis Absent Likely present
Dyspnea On walking On talking At rest
Speaks In sentences Phrases In words
Pulse Normal Mild tachycardia Marked tachycardia
(> 180bpm in young)
Pulsus paradoxus Normal Less than 20 mmHg 20-40 mmHg
Wheezes End expiratory Holo expiratory Exp and inspiratory
May be quiet
Retractions Absent Common Usual
Peak expiratory flow 70% 40-69%* <40%*
Oximetry in air > 95 % 90 –95 % < 90%
PaCO2 < 42 mmHg* > 42 mmHg
PaO2* Normal* < 60 mmHg
* Means test not usually necessary
Signs of acute severe asthma with imminent respiratory arrest
Drowsy or confused
Paradoxical thoracoabdominal movement
Absence of wheeze
Bradycardia, Absent pulsus paradoxus (due to respiratory muscle fatigue)
Status asthamticus : A severe asthma exacerbation that does not improve with
standard therapy

Page | 184
Action plan
Pulse oximetry in air

High flow oxygen to keep O2 saturation > 92%
SABA (Salbutamol): 2.5 - 5 mg with saline by nebulizer or 2 to 6
puffs by MDI plus spacer
(Repeat every 20 minutes for the 1st hour)
Ipratropium bromide: 125 - 250 mcg by nebulizer; if no adequate
response to the first salbutamol nebulizer
(Repeat every 20 minutes for the first hour only)
Oral Corticosteroids (1-2mg/kg in divided doses) in moderate to
severe asthma exacerbations to hasten recovery and prevent
recurrence of symptoms
Epinephrine( 1:1000) :0.3-0.5 mg IM or SC may be given in
severe cases
Outcome at 1 hour
Good outcome: Moderate to severe

Normal physical findings exacerbations that do not
PEF >70% of predicted or personal best adequately improve within
Oxygen saturation >92% in room air for 1-2 hr of intensive treatment
4 hr High risk patients*
1. :HDQJUDGXDOO\ĺ6$%$every 3-4 hr
2. ,IRQDFRQWUROOHUGUXJ ,&6 ĺFRQWLQXH
Admission
it during and after exacerbation
3. Continue oral steroids for 3-7 days
* High risk patients include:

Previous severe asthma exacerbation (intensive care unit admission)
Two or more hospitalizations for asthma in past year
Three or more emergency department visits for asthma in past year
Low birthweight
Poverty
(Nelson Text Book of Pediatrics, 2016)

Page | 185
C. Admission to hospital /PICU

Admission to an PICU is indicated for patients with
Severe respiratory distress
Concern for potential respiratory failure and arrest
Action plan
Cardio-pulmonary monitoring
Oxygen
Salbutamol
Nebulizer every 20 min as needed, then every 1-4 hr as needed
Or
Continuous nebulization with oxygen: 5-15 mg/hr
Corticosteroids: Short course 3-7 days
Oral: Prednisone 1-2 mg/kg
Parenteral: Methyleprednisolone or Hydrocortisone
Ipratropium bromide nebulizer (poor evidence; no longer recommended)
Persistent severe dyspnea and high-flow oxygen requirements
R Obtain IV access, take electrolytes , glucose and ABG

R CXR in life threatening attack or suspected pneumothorax (deteriorate after
a period of improvement)
R Start IV maintenance fluids
Dextrose 5% in 0.45% saline with 20-mmol/l kcl
At 70-80% of maintenance
Correct any dehydration
R Replace nebulizer by IV Salbutamol ; Watch for low potassium and ECG
monitoring for arrhythmias
Critically ill or at risk for respiratory failure

Available options
x Epinephrine IM or SC
x Magnesium sulphate (25-75 mg/kg, maximum dose 2.5 g, given
intravenously over 20 min)
x Aminophylline ; loading dose 5-10 mg/kg over 1 hour followed by
maintenance 1 mg /kg/hour (0.7 mg /kg/hour if >10 years)
x Inhaled heliox (helium and oxygen mixture)
x Assisted /mechanical ventilation

Page | 186
After exacerbation resolution:

1. Space SABA gradually
2. Continue steroids for full 3-7 days
3. Start controller therapy
4. Families of all children with asthma should have a written action plan to
guide their recognition and management of exacerbations
5. With history of life-threatening episodes, especially if abrupt-onset in
nature, providing an epinephrine autoinjector and, possibly, portable
oxygen at home should be considered
(Nelson Text Book of Pediatrics, 2016)

3
Long term asthma management

I. Assessing asthma severity and initiating treatment (For patients who are not currently taking long-term control medications)
Persistent
Intermittent Mild Moderate Severe
1. Daytime symptoms
2 days/wk > 2 days/wk but not daily Daily Throughout the day
(Wheezing, cough, breathless)
2. Nocturnal symptoms /awakening (Nocturnal cough, wheezing, breathless)
Age < 5 yr 0 1-2 /mo 3-4 /mo >1 /wk
$JH\U 2 /mo 3-4 /mo >1 /wk Often 7 /wk
3. Need for reliever 2 days/wk > 2 days/wk Daily Several times per day
4. Limitation of activities
(Cough ,wheeze, or breathless None Minor limitation Some limitation Extreme limitation
on exercise, play or laugh)
5. Lung function (FEV1);
> 80% predicted 80% predicted 60-80% predicted < 60% predicted
age 5 yr
Recommended step for
Step 1 Step 2 Step 3 Step 3 or Step 4
initiating therapy
2
II. Stepwise Approach for Managing Asthma in Children

Step 1 Step 2 Step 3 Step 4 Step 5 Step 6
Rescue treatment for all steps: As needed inhaled VKRUWDFWLQJȕDJRQLVW 6$%$ 6KRUWFRXUVHRIRUDOVWHURLGV if exacerbation is severe or
history of previous severe exacerbations
Move to step 2 if : Low dose ICS Medium dose ICS Medium dose ICS High dose ICS High dose ICS
Rescue treatment is
needed more than Or + Montelukast* + Montelukast* + Montelukast*
twice a week Montelukast OR OR OR
or
If night-time OR Medium dose ICS High dose ICS High dose ICS
symptoms at least Low dose ICS + + LABA + LABA + LABA
once a week *
or Montelukast +
If exacerbation OR Oral glucocorticoids
in the last 2 years Low dose ICS + LABA lowest dose
Modified-release oral theophylline may substitute Montelukast
Consider Anti IgE(Omalizumab) for patients
above 12 years with Allergies
Consider subcutaneous allergen immunotherapy for patients who have allergic asthma
Patient education, environmental control, and management of comorbidities
*
For those less than 4 years
Step Down or Step Up gradually

According to assessment of current clinical control (See next table)
3
III. Assessment of current clinical control (preferably over 4 weeks)
Characteristic Well controlled Not well controlled Very poorly controlled
(All of the following) (Any measure in any week)
Daytime symptoms None or < 2 /week; very short >2 days/wk Throughout the day
Nocturnal symptoms /awakening
Age < 5 yr 1 /mo > 1 /mo >1 /wk
$JH\U 1 /mo 2 /mo 2 /wk
Limitation of activities None Some limitation Extreme limitation
Need for reliever 2 days/wk > 2 days/wk Several times per day
Lung function (FEV1 or PEF) > 80% predicted 60-80% predicted < 60% predicted
Exacerbations requiring systemic 0-1/yr 2/yr > 3/yr
steroids courses
Step Down gradually to the least Step Up gradually after checking inhaler technique,
medication necessary to maintain adherence, environmental control, and comorbid
Action
control if asthma is well condition
controlled at least 3 months Improvement should be seen within 4-6 weeks
Page | 190
IV. Avoid exposure to triggering agents

Eliminate or reduce problematic environmental exposures
Avoid drugs, foods, and additives known to cause symptoms.
Avoid allergens as suggested by skin testing
Treat co-morbid conditions: sinusitis, GERD and rhinitis.
Give annual influenza vaccine unless egg allergic
In exercise induced asthma give:
SABA inhalation o 10 minutes before exercise
or Montelukast oral o 1 hour before exercise
V. Patient education
x Explain basic facts about asthma
x Written asthma management plan
x Demonstrate optimal technique of use of asthma devices
x Insist on adherence to medications
x Ensure avoidance of risk factors
x Two to four asthma checkups per year for:
1. Frequency of asthma symptoms during the day, at night, and with
physical Exercise
2. Frequency of “rescue” SABA medication use and refills
3. Lung function measurements (spirometry) for older children at least
annually
4. Number and severity of asthma exacerbations
5. Presence of medication adverse effects since the last visit

Page | 191
Differential diagnosis of asthma

(Wheezy Chest)
Definition of wheeze
- Expiratory musical continuous sound
- Due to partial obstruction of small bronchi & bronchioles
- Can be sibilant or sonorous
- May be also inspiratory in severe obstruction
Possible mechanisms
- Bronchoconstriction (spasm of airways smooth muscles)
- Bronchial mucosal edema.
- Excessive, viscid secretions inside airways lumens
Causes
Acute Chronic /recurrent

Acute bronchiolitis. Bronchial asthma
Bronchial asthma exacerbation Congestive heart failure
Foreign Body inhalation Cystic fibrosis
Congestive Heart failure(e.g. Dynamic airway collapse: e.g.
congenital heart diseases or bronchomalacia &tracheomalacia
cardiomyopathy) Recurrent aspiration e.g.
Aspiration e.g. GERD GERD
Tracheo esophageal fistula
Neuromuscular disorders
Foreign body
Pulmonary tuberculosis(LN+)
Airway compression by: lymph
nodes, vascular ring or tumor


Page | 192
Foreign body aspiration

Clinical picture
Squeals
1. Immediate expelling by cough reflex
2. Retained foreign body: manifestations differs according to site
Type of obstruction Laryngeal Tracheal Bronchial
Partial - Respiratory distress - Metallic cough - Chest
- Stridor wheezes
- Hoarsness of voice
- Aphonia
Complete - Suffocation - Respiratory distress - Collapse
- Cyanosis - Abscess
- Pneumonia
History
Commonly reported in children 3months to 6 years
History of sudden chocking or frank history of foreign body aspiration
Triphasic history may be obtained:
- Initial phase: cough, chocking, stridor or gagging
- Silent phase: if foreign body pass and impact in smaller airways
- Phase of complications: recurrent pneumonia , abscess, bronchiactasis
Signs
R Fixed localized wheeze; unresponsive to treatment.
R Unexplained lung collapse
R Diminished breath sound over one lung, one lobe or one segment
R Mediastinal shift (unilateral collapse or emphysema).
R “Same site” recurrent pneumonia, abscess, bronchiectasis
Chest X-ray
- Positive only in about 50% of cases
- May show obstructive collapse or obstructive emphysema in expiratory film.
Treatment
A. Without respiratory distresso bronchoscopic extraction
B. With respiratory distress:
1. If the child is breathing well:
- Encourage cough to clear the foreign body
- Be vigilant for any deterioration
2. If cough becomes ineffective:
Try to assist expulsion of the foreign body
Provide rescue breathing in between trials.

Page | 193
Use the Alert, Verbal, Pain, Unresponsive pediatric scoring system(AVPU)

to determine both a child’s level of consciousness and cerebral cortex
function
If trials fail and infant becomes unconscious, attempt to visualize foreign
body and remove manually.

i. First aid for the choking infant < 1 year of age
Hold infant prone with the head down.
Give 5 interscapular back blows, using heel of hand.
Turn the infant supine, with head dependent and perform
5 quick downward chest thrusts .
ii. First aid for the choking child older than 1 year of age
A) In conscious patient abdominal thrust in sitting or
standing (Heimlich maneuver):
Encircle the child chest with arms from behind.
Place one fist against patient’s abdomen in midline
just below tip of xiphoid.
Grasp fist with other hand and exert 5 quick, upward
thrusts.
B) In unconscious patient abdominal thrust in lying down:

Place the patient supine.
Open patient airway using chin lift or jaw
thrust.
Place heel of one hand on child’s abdomen
just below costal margins.
Place the other hand on top of the first hand.
Press both hands into abdomen with quick,
upward thrusts in midline.
iii. Further interventions

- Laryngoscopic removal.
- If failed; push foreign body more distally.
- If failed, perform immediate cricothrotomy
Prevention
Avoid chocking materials in infants and young children e.g. small toys, nuts,
popcorn

Page | 194
Dry Pleurisy
Definition: Fibrinous inflammation of the pleura.
Causes
Infections: Viral pneumonia, bacterial pneumonia, tuberculosis
Chest wall trauma
Collagen diseases e.g. Rheumatic fever, systemic lupus erythematosus
Clinical picture
R Manifestations of the cause
R Chest pain: Stitching, n with deep respiration, cough & sneezing
R Patients may prefer to lie on same side.
R Auscultation: Pleural rub: - Scratchy sound.
- Decrease by holding breathing.
Treatment: - Treat the cause.
- Analgesics.
Serofibrinous Pleurisy
(Pleural Effusion)
Normally, only 4-12 mL of fluid is present in the pleural space, but if
formation exceeds clearance, fluid accumulates.
Definition: Serofibrinous inflammation of the pleura.
Types of effusion
Transudate Exudate Bloody Cheylous
Characters
- Clear; straw colored - Turbid ; opaque Bloody with RBCs - Milky white
- Proteins < 3gm/dl - > 3 gm/dl. on mic. examination - Dissolved with
- p Cells (mesenchymal) - n Cells (PMNLs) ether
- p Specific gravity - n Specific gravity (>1015) - Spread on filter
- Sterile - May reveal organisms paper
- pLactate dehydrogenase - Lactate dehydrogenase >200 iu /l
Mechanisms
- Increased hydrostatic Increased capillary permeability Impaired lymphatic
capillary pressure due to inflammation , malignancy, drainage
- Decreased plasma mediastinal or chest wall diseases
osmotic pressure
Causes
Passive transudation in - Pneumonia. - Tumors Thoracic duct
renal, cardiac & hepatic - T.B. - Trauma obstruction or
causes of generalized - Ruptured Lung abscess - Hemorrhagic blood trauma
edema - Mediastinitis Diseases
- SLE, uremia, metastasis
- T cell lymphoma.

Page | 195
Clinical picture
Symptoms
Manifestations of the underlying cause (e.g. fever, dyspnea,.….)
Respiratory distress
Chest pain: dull aching pain; patient prefers to lie on the affected side
Chest examination
Small effusion:
Clinical picture of an underlying cause e.g. pneumonia o
bronchophony, bronchial breathing and crepitation
Massive effusion
Inspection o Unilateral bulge, full intercostal spaces with
diminished movement
Palpation o Decreased TVF & trachea shifted to opposite side
Percussion o Stony dullness, rising to axilla
Auscultation o Marked diminished breath sounds (or absent).
o Aegophony (nasal tone of voice) may present at
the top of effusion due to kinked bronchi
Investigations
1. Chest X-ray in supine and upright positions:
In small effusion: homogenous opacity just obliterating costophernic angle
In moderate to large (Massive) effusion: homogenous opacity
- Filling the costophernic angle
- Rising to the axilla.
- With shift of the mediastinum to the opposite side
Mild left sided effusion Moderate right sided effusion Massive left sided effusion
2. Chest ultrasonography
Diagnostic for pleural fluid
Guide thoracentesis/ Chest tube insertion

Page | 196
3. Thoracentesis:
a. Inspect the fluid:
- Straw colored o Transudate
- Turbid o Exudates
- Milky white o Chylous
- Fetid odor o Anaerobic infection , empyema
b. Cytology:
- Polymorph o Infection e.g. Pneumonia , early TB
- Lymphocytes o TB, chylous , malignancy ; lymphoma
- Esinophils o Parasitism, emboli
- Red cells o Trauma, tumors,……
c. Order culture & sensitivity
d. Biochemical examination: Mention from previous table
4. Tests for TB: tuberculin test, sputum analysis and culture
5. Pleural biopsy, thoracoscopy and/ or broncoscopy: if TB or malignancy is
likely
Outcome of effusion
Massive effusion may impair cardiac function
Secondary pyogenic infectiono empyema
Organization of unresolving exudates may lead to fibrothorax
Treatment
1. Treat the cause
2. Thoracocentesis is both diagnostic and therapeutic
3. Thoracostomy tube drainage
Closed drainage using intercostal tube with underwater seal
Indicated for:
a. Massive effusion
b. Marked respiratory distress
c. Effusion not resolved with medical treatment
d. Empyema
Site of aspiration o 5th space mid axillary line
Ӌ

Page | 197
Purulent Pleurisy (Empyema)
Definition
Exudative pleural effusion with marked nn pus cells
“Effusion is empyema if bacteria are present on Gram staining, pH is < 7.20,
and there are >100,000 neutrophils/ȝL”
Causes
Pneumonia (Pneumococci, Staph, H. influenza and klebseilla).
Rupture lung abscess.
Rupture abdominal abscess or subphernic abscess
Rupture of chest wall abscess
Secondary contaminated chest trauma or surgery
Secondary infection of an effusion
Secondary to infection from suppurated lower cervical lymph nodes
Clinical picture
1. Acute empyema: Same as pleural effusion with:
- High fever, toxic patient.
- Same side chest wall edema
- High incidence of complications.
2. Chronic empyema; empyema lasting for 3 months or more:
Clinical Laboratory
Pale clubbing Anemia of chronic illness ;
Pallor normocytic normochromic
Low grade fever (Pyrexia) Elevated ESR
Eventual fibrothorax ,collapse, Poly morph nuclear
with same side mediastinal shift , leucocytosis
scoliosos and narrow ribs
Risk of amyliodosis
Complications
1. Local spread to:
Lung o Bronchopleural fistula.
Abdomen o peritonitis.
Chest wall o empyema necessitatis.
Pericardium o purulent pericarditis.
2. Distant spread e.g. Meningitis, septicemia,…..
Investigations
1. Chest X-ray: as effusion but;
Opacity is denser.
Ribs crowding
May be lung collapse in chronic cases

Page | 198
2. Thoracocentesis
For character of the fluid (exudate with nn pus cells).
For culture & sensitivity.
3. Ultrasonography or CT chest: Detect pleural fluid septa and loculated
empyema
4. Blood cultures: have a higher yield than cultures of the pleural fluid.
Treatment
1. Thoracostomy tube drainage
Closed drainage using intercostal tube with underwater seal(Open
drainage may be necessary in chronic cases)
For about 1 week
More than one tube may be needed to drain pockets of pus.
Use intra pleural fibrinolytic agents (Streptokinase or Urokinase):
For 3-5 days
Promote drainage, decrease fever, and shorten hospitalization
Precaution: risk of anaphylaxis, and hemorrhage
2. Antibiotics: According to culture and sensitivity for 2- 4 weeks

3. Surgical decortications
Via video-assisted thoracoscopic
surgery (VATS) or open thoracotomy
Indicated for child who remains
febrile and dyspneic >72 hr after
initiation of therapy with intravenous
antibiotics and thoracostomy tube
drainage
N.B: 3VHXGRFK\ORXVHIIXVLRQ: Chronic serous effusion with cellular
degeneration:
Criteria: - High cholesterol /Low triglycerides level.
- Doesn’t clear with ether or alkali.
- Doesn’t spread on filter paper

Page | 199
Hydropneumothorax
Definition: Presence of both fluid & air in the pleural cavity.

Causes
Thoracocentesis for pleural effusion o hydropeumothorax.
Thoracocentesis for hemothorax o hemopneumothorax.
Empyema with bronchopleural fistula o pyopneumothorax
Clinical picture
Chest examination
- Inspection o Unilateral bulge.
- Palpation o Decreased TVF & trachea shifted to opposite side.
- Percussion o Shifting dullness.
- Auscultation o Marked diminished breath sounds.
o Succession splash
Investigations
- As pleural effusion;
- Chest X-ray o air- fluid level
Treatment
1- Antibiotics according to culture and sensitivity.
2- Closed drainage with underwater seal If failed o surgical closure of the
fistula.

Page | 200
Pneumothorax
Definition: Presence of air in the pleural cavity
Causes
Rupture preumatoceles
Rupture tuberculous cavity
Rupture lung abscess.
Rupture surface alveoli in air trapping
Vigorous resuscitation
Chest wall trauma
Clinical picture
Symptoms
Asymptomatic (in small pneumothorax) o discovered accidentally
Symptomatic: o Respiratory distress (nn with tension pneumothorax).
o Symptoms of the cause
Chest examination
- Inspection o Unilateral decreased movement & unilateral bulge.
- Palpation o Decreased TVF & trachea shifted to opposite side.
- Percussion o Hyper resonance.
- Auscultation o Marked diminished breath sounds.
o Coin test
Evidence of tension
Mediastinal shift
Circulatory compromise
Hearing a “hiss” of rapid exit of air under tension with the
insertion of the thoracostomy tube
Investigations
Chest X-ray/CT o jet black opacity
± mediastinal shift to the opposite
side
CT chest: may identify underlying
pathology such as blebs
For the cause
Treatment
1- Small pneumothorax: usually resolve within 1 week.
2- Symptomatic:
- Closed drainage with underwater seal.
- Tube is inserted in the 2nd space mid clavicular line.
3- Treat the underlying cause.

Page | 201
Tuberculosis
Definition
Chronic infectious disease caused by Mycobacterium TB bacilli (human and
bovine types) which is alcohol and acid fast aerobic intracellular bacilli.
Modes of transmission
Inhalation o pulmonary tuberculosis
Ingestion(with milk) o intestinal T.B(& tonsillar tuberculosis)
Wound contamination o cutaneous tuberculosis
Hematological spread form primary T.B. focus
Risk factors
Children exposed to high-risk adults
Low Socioeconomic standard (Homeless persons)
Suppressed immunity e.g. HIV, malnutrition & immunosuppressive therapy
Susceptible age: disease is more severe in infants and young child
Susceptible Race: More in Negroes
Pathogenesis
Primary exposure to T.B bacilli result in formation of primary complex at the
site of entry of the bacilli (the commonest form in children).
1. Primary pulmonary complex:
Composed of Primary focus (Ghon’s focus)
Lymphangitis
Hilar lymphadenitis
2. Primary cervical complex (tonsillar T.B)
Composed of Primary focus in tonsils
Lymphangitis
Cervical lymphadenitis
3. Primary intestinal complex
Composed of Primary focus in pyere’s patches
Lymphangitis
Mesenteric lymphadenitis
Each primary focus is formed of tubercles each tubercle is formed of :

- Central caseation
- Epitheloid cells
- Macrophages and lymphocytes
- Langerhans giant cells

Page | 202
Fate of primary pulmonary complex
With good immunity With poor immunity
Regression (in 90%) Progression

x Small focus o complete fibrosis
x Large focus o capsulation & calcification o
In which T.B bacilli may remain viable
for years ;Latent TB Infection ( LTBI)
N.B: Risk for progression of latent TB: Infants and children 4
yr of age, especially those <2 yr of age, Adolescents and young
adults, immunocompromised, and infection with measles
and pertussis.
Primary Direct spread Bronchial spread Hematologic spread

Cavitation (Endobronchial T.B)
T.B pneumonia Incomplete obstruction One organ T.B

Tuberculous effusion o emphysema Miliary T.B
Complete obstruction
o collapse
Ț


Page | 203
Clinical Picture
1.Pulmonary TB
Common
9 Asymptomatic in up to 50%; may be mild fatigue & poor appetite
9 Nonproductive cough and mild dyspnea are the most common symptoms
9 Some infants have difficulty gaining weight or frank failure-to-thrive
May be
Hilar lymphadenopathy may present with:
Obstructive emphysema/wheezing: due to partial bronchial obstruction
Lung collapse: due to complete bronchial obstruction
Positive D’Espine sign (Bronchial breathing below level of tracheal
bifurcation)
Wheezy chest : due to endobronchial TB with partial bronchial obstruction
Allergic manifestations:
R Erythema nodosum R Phlyctenular keratoconjunctivitis

Toxic manifestations (uncommon) o night fever & sweating.
Manifestations of extension; usually with toxic manifestations and hectic
fever e.g. Bronchopneumonia, tuberculous effusion, miliary tuberculosis
N.B. Cough with sputum is rare, seen literally in progressive primary
pulmonary TB with formation of T.B cavity.
2. Extra pulmonary tuberculosis
A. Tuberculous lymphadenopathy
Common sites: Cervical, Mediastinal, Mesenteric
Criteria:
Firm
Non-tender
Early discrete then matted after caseation
Complications:
Cold abscess
Draining sinus
Diagnosis: Biopsy and histologic examination

Page | 204
B. Miliary tuberculosis
Hemtogenous spread of tubercle bacilli from any focus (usually
pulmonary) o causing disease in 2 or more organs; lung, kidneys, liver,
spleen, bone marrow meninges.
Usually complicates the primary infection, occurring within 2-6 mo of the
initial infection
Common in
Infants, malnourished, immunosuppressed, with measles or pertussis
Clinical picture
Often, the onset is insidious, with anorexia, weight loss, and low-grade
fever
Weeks later:
Generalized lymphadenopathy and hepatosplenomegaly
Fever higher and more sustained
Weeks later:
The lungs become filled with tuberclesĺ dyspnea, cough, rales, or
wheezing. May be respiratory distress, hypoxia, and pneumothorax
Meningitis (recurrent headache) or peritonitis (abdominal pain) are
found in 20-40%
Cutaneous lesions include papulonecrotic
tuberculids, nodules, or purpura
Diagnosis
1. History of recent exposure to an adult with
infectious TBĺ The most important clue
2. Biopsy of the liver or bone marrow with appropriate bacteriologic and
histologic examinations more often yields an early diagnosis
3. Chest x ray/CT:
Small miliary shadows;
< 2-3 mm
(Snow storm opacities)
4. Fundus examination:
Show choriod tubercles in 13-87 %
Highly specific
5. TST is non-reactive in 40 %

Page | 205
C. Tuberculous meningitis
Complicates about 0.3% of untreated tuberculosis infections in children
Due to hematogenous spread either isolated or as a part of miliary TB
Tubercle bacilli spreading into the subarachnoid space form a gelatinous
exudate that infiltrates the corticomeningeal blood vessels, producing
inflammation, obstruction, and subsequent infarction of cerebral cortex
Clinical picture
- In infancy and early childhood
- Insidious onset
- Pass in 3 stages (each lasts 1-2 weeks)
1st stage 2nd stage 3rd stage

(Nonspecific) (Meningitis) (Terminal stage)
Fever Meningeal irritation Hemiplegia or paraplegia
Headache, irritability Ĺ Intra cranial tension Coma
Drowsiness, and Cranial nerve palsies Eventually death
malaise
D. Intestinal tuberculosis
Occur secondary to
Ingested tubercle bacilli in milk
Swallowed sputum from tuberculous lesions in the lungs
Clinical picture
Tabes mesentrica; enlarged mesenteric lymph nodes.
Tuberculous enteritis:
Chronic diarrhea o failure to thrive
Chronic abdominal pain
E. Tuberculous peritonitis
Occur 2ry to: Spread from intestinal or genitourinary T.B lesions
Clinical picture
Ascites
May be adhesions.
F. Pott’s disease
Common sites: mainly affect lower dorsal spine.
Clinically
Back pain and stiffness
Cold abscess formation with persistent angular kyphosis
X ray spine: Diagnostic

Page | 206
Diagnosis of tuberculosis
1. History of recent exposure to an adult with infectious TBĺ The most
important clue
2. Tuberculin Skin Test (TST):
Detects delayed hypersensitivity reaction to tuberculoprotein
Mantoux test: intradermal injection of 0.1 ml containing 5 tuberculin units
of purified protein derivative (PPD).
Interpretation: measure the induration after 48 -72 hours
Indications : see later
A. Positive test (= TB infection or disease)
1. Induration t 5 mm2 in high risk patients;
Close contact with active tuberculosis patient
Immunodeficiency
Child having clinical or chest x ray compatible
with tuberculosis
2. Induration t 10 mm2 in moderate risk patients;
Child < 4 years
Child from endemic area or exposed to people from endemic area
Chronic diseases with increased risk e.g. diabetes , renal diseases
3. Induration t 15 mm2 in any child above 4 years without risk factors
B. False positive test; usually less than 10 mm induration, consider:
Recent BCG vaccination; reactivity is lost by 5-10 years after vaccine
Non tuberculous mycobacteria
C. Negative test: induration less than 5 mm2
True negative test o no T.B infection
False negative test o in
Technical error
Transient suppression of tuberculin reactivity with viral infections
e.g. measles, mumps or live virus immunization
Early in the disease
Miliary TB.
Immunodeficiency
3. Interferon-ȖRelease Assays (IGRA)

Ț

Page | 207

Indications of TST or IGRA

1. Contacts of people with confirmed or suspected contagious TB
2. Children with radiographic or clinical findings suggesting
tuberculosis
3. Children immigrating from countries with endemic infection (e.g.
Asia, Middle East)
4. Children with travel histories to countries with endemic infection
5. Children infected with HIV should have annual TST or IGRA
6. Before initiation of immunosuppressive therapy e.g. Prolonged
steroid

Ӌ

Ӌ

4. Specific:
A. Pulmonary tuberculosis
1. Isolate M. tuberculosis:
Sampling
Expectorated sputum in older children
Induced sputum with a jet nebulizer and chest percussion followed by
nasopharyngeal suctioning is effective in children as young as 1 year
3 consecutive early morning gastric aspirate before the infant has arisen
Workup
Acid-fast bacilli staining (Zehl Nelsen stain and light microscopy)
Culture
Polymerase chain reaction ;PCR(of limited value)
Recently , Gene Xpert MTB/RIF is a real-time PCR assay for M.
tuberculosis that simultaneously detects rifampin resistance

Page | 208
N.B For many forms of tuberculosis, the culture yield is only 25-50%. So,
negative cultures never exclude the diagnosis of tuberculosis in a child.
2. Chest X-ray: May reveal
Enlarged hilar lymph nodes Miliary TB; small miliary shadows 1-2
Localized emphysema mm (snow flake opacities).
Enlarged hilar lymph nodes T.B bronchopneumonia ;fluffy cotton

Localized collapse appearance
Pleural effusion Calcified granuloma (primary focus)

Page | 209
3. Detect the pathology:

Pleural biopsy
Lymph nodes biopsy
Bronchoscopy (for suspected endobronchial TB)
and biopsy
4. Pleural fluid examination:
Color : Yellow with blood tinge
Characters: Usually unilateral, massive; recollect after aspiration
Cells : n lymphocytes but it is very rare to discover T.B bacilli
Cultures of the fluid are positive in <30% of cases.
5. Blood: Elevated ESR
B. Tuberculous meningitis
Lumbar puncture and CSF analysis, culture and PCR(See neurology)
CT, MRI may detect tuberculoma; a tumor-like mass resulting from
aggregation of caseous tubercles
MRI of brain of a 3 yr old

child showing multiple
pontine tuberculomas
(Nelson 2016)
N.B The TST is nonreactive in up to 50% of cases, and 20-50% of children

have a normal chest radiograph.
C. Intestinal tuberculosis:
Mesentric lymph node biopsy
Ascitic fluid analysis
The presence of a positive TST or IGRA, an abnormal chest

radiograph consistent with tuberculosis, and history of exposure to
an adult with infectious tuberculosis is adequate for the probable
diagnosis of tuberculosis disease

Page | 210
Treatment
Prevention
* BCG vaccine (see before)
* Milk sanitation (boil milk for10- 15 minutes before use)
* Isolate and treat infective cases with open pulmonary TB.
* Avoid contact with cases.
* Window prophylaxis:
For children who:
Have unavoidable close contact to an adult with potentially contagious
tuberculosis disease and
Have a negative TST or IGRA result
Break the contact with the source case for tuberculosis (i.e. physical
separation or adequate initial treatment of the source case) and Give INH
10 mg/kg/d for 3 months (the time delayed hypersensitivity develops)
Perform TST or IGRA at 3 months
If positive result ( t 5 mm2 ) ĺ continue INH for 9 months
If negative resultĺVWRS INH and INH resistant BCG can be given
Trace the possible adult source and treat adequately to prevent other
secondary cases.
Curative
A. General lines
Good nutrition, fresh air
Follow up carefully to promote adherence to therapy, and to monitor for
toxic reactions to medications
B. Anti-Tuberclous drugs
First line drugs
Drug Daily Twice weekly Side effects
dose* dose *
Isoniazide 10-15 Double the - Hepatotoxic
(INH) dose - Peripheral neuritis (?? add vit B6)
Rifampicin 10-20 Same - Hepatotoxic
- Red staining of secretions
Pyrazinamide 20-40 50 - Hepatotoxic
- Hyperuricaemia
Ethambutol 20 50 - Optic neuritis (usually reversible)
- Color blindness (green,red)
* mg/kg

Page | 211
Alternative drugs
Used as additive drugs in
Multiple drug resistant tuberculosis
Life threatening tuberculosis e.g. T.B. meningitis.
Drug Dose (mg/kg/d) Side effects
Streptomycin 20-40 (I.M) Ototoxic & nephrotoxic
Ethionamide 15-20 (oral) Hepatotoxic (similar to INH).
Amikacin 15-30 (IM) As streptomycin
Regimens for treatment
The specific treatment plan must be individualized for each patient according to
the results of susceptibility testing on the isolates from the child or the adult
source case
1. Six months regimen
Standard therapy for intrathoracic tuberculosis and cervical
lymphadenopathy
Rifampicin and INH (for 6 months) + Pyrazinamide and Ethambutol (in
the1st 2 months) 1. Rifampicin
2. INH
3. Pyrazinamide
4. Ethambutol Rifampicin + INH
For 2 months For 4 months
When directly observed therapy is used: initial period as short as 2 wk of

daily therapy followed by intermittent (twice weekly) therapy is as
effective as daily therapy for the entire course.
2. Nine month regimen
Using only isoniazid and rifampin
Highly effective for drug-susceptible tuberculosis
Carry risk of initial drug resistance and poor compliance
3. In miliary T.B, meningitis and bone T.B
Extend treatment period for 9-12 months.
4. In drug resistance
Treatment is undertaken by a clinician with specific expertise
Initial treatment
Isoniazid resistance 9 mo with rifampin, pyrazinamide, and
ethambutol
Isoniazid and rifampin resistance extend total duration of therapy
to 12-24mo, and avoid twice-a-week regimens
5. Latent TB infection: isoniazid for 6-9 months

Page | 212
Steroids in T.B
Used in
1- Miliary tuberculosis o to improve the general condition
2- Endobronchial tuberculosis with localized emphysema.
3- Enlarged hilar lymph nodes with airway obstruction.
4- Tuberculosis of serous cavities e.g Pleurisy , Pericarditis , Meningitis
5- Adrenal tuberculosis
Precautions
1- Under umbrella of antituberculous drugs.
2- Dose 2 mg/kg/d for 4-6 weeks followed by gradual tapering.

Page | 213
Respiratory failure
Definition: Failure of the lungs to keep normal level of arterial blood gases( O2 & CO2)
Peripheral(type I) Central (type II)
Causes - Airway obstruction e.g asthma - Brain : hemorrhage,drugs
- Pneumonia - Neuromuscular: spinal muscle
- Pneumothorax atrophy, Guillian Barre syndrome
- Massive effusion - Skeletal: severe kyphosis, scoliosis
Clinically * Manifestations of the cause * Manifestations of the cause
* Respiratory distress * Irregular , shallow respiration
* Mainly hypoxemia: irritability * Mainly hypercapnia: cyanosis,
restless, dizziness , cold pale lethargy, headache and impaired
extremities consciousness
ABGs pPaO2 – nPaCO2 – ppH
Treatment Treat the cause Treat the cause
Oxygen therapy(See neonates) Ventilation

‫‬
‫\‪ 1HSKURORJ‬‬
Page | 214

Structure of the Nephron
x Nephrons are the structural and functional units of the kidneys that carry out
processes that form urine
x Each nephron consists of a renal corpuscle composed of a tuft of capillaries (the
glomerulus), surrounded by a glomerular capsule (Bowman’s capsule) and a renal
tubule. The renal tubule begins at the glomerular capsule as the proximal
convoluted tubule, the loop of Henle, and turns into a distal convoluted tubule
before emptying into a collecting duct.
x The collecting ducts collect filtrate from many nephrons, and extend through the
renal pyramid to the renal papilla, where they empty into a minor calyx
Note: - Efferent arterioles provide blood supply to the whole renal tubules
- Erythropoietin is produced by peritubular capillary endothelium cells

Page | 215

Functions of the Nephron
Glomerular filtration: Reabsorption at the PCT (Main bulk)
Plasma is passively filtered through the Sodium: 65-70% of filtered by active
glomerular capillary walls. transport by Na-K pump
The ultrafiltrate, which is cell free, Water :By osmosis (65-70% of filtered
contains all of the substances in plasma water) as obligatory water
(water,electrolytes, glucose, phosphate, reabsorption
urea, creatinine, peptides, low HCO3: Linked to sodium transport
molecular weight proteins) except Nutrients :100% of glucose, amino
proteins having a molecular weight of acids, vitamins by secondary active
Ӌ68 kd (e.g. albumin and globulins). transport
Phosphate (80% reabsorbed )
Loop of Henle: Ions: Ca,Mg,K by passive diffusion
Na,K,Cl:
active Distal tubules :( DT)
transport by Early DT has Na+-Cl-
Na-K-2Cl cotransporters (inhibited
cotransporter by Thiazide diuretics)
in ascending Late DT has Na+ (and
limb(These K+) channels that are
transporters increased by aldosterone
are the targets hormone (inhibited by K
for loop sparing diuretics e.g.
diuretics Ameloride).Net result is
e.g Furosemide) Na reabsorption and
Water :By secretion of either K+ or
osmosis (10% H+ and
of filtered Water reabsorption
water) in follows Na
descending Reabsorption of Ca
limb helped controlled by parathyroid
by ADH hormone
Collecting ducts:
x Like late DT, the collecting tubule has Na+ (and K+) channels induced by Aldosterone
x Water reabsorption secondary to Na reabsorption and passive osmosis 2ry to interstitial
hypertonicity with help of Antidiuretic hormone
Summary of renal functions:

1. Control body water
2. Get rid of waste e.g. Blood urea nitrogen , creatinine, H+, excess K+, Drugs
3. Regulation of acid –base balance by:
R About 90% of filtered bicarbonate is absorbed in the proximal tubule aided by
carbonic anhydrase (CA)
R Secretion of hydrogen ion as titratable acid or as NH4+ at the distal tubule
4. Hormonal role e.g. Release of Erythropoietin, Activation of vit D

Page | 216
Estimation of Glomerular Filteration Rate (GFR)

- Formation of nephrons is complete at 36-40 wk of gestation, but functional
maturation with tubular growth and elongation continues during the 1st decade of
life
- Because new nephrons cannot be formed after birth, any disease that results in
progressive loss of nephrons can lead to renal insufficiency
Serum creatinine:
x Estimates the GFR in the steady state
x Insensitive measure of decreased renal function because its level does not rise
above normal until the GFR falls by 30-40%
Clearance tests (require timed urine collection)
The clearance is represented by the following formula:
Cs (mL min) = Us (mg mL) × V (mL min) Ps (mg mL)
Where Cs equals the clearance of substance s, Us reflects the urinary
concentration of s, V represents the urinary flow rate, and Ps equals the
plasma concentration of s.
To correct the clearance for body surface area, the formula is
Corrected clearance (mL/ m/1.73m2) = C (ml/min) ×1.73/Surface area (m2)
Clearance substances
- Exogenous: Inulin clearance (Gold standard – Difficult)
- Endogenous: Creatinine clearance
Formula in pediatrics:
1. Haycock-Schwartz formula
eGFR = k × ht / Pcr
eGFR Estimated glomerular filtration rate(in ml/min/1.73m2)
k Empirical value relating height to muscle mass
= 0.33 for LBW infant
= 0.45 for Full term infant
= 0.55 for child or adolescent girl
= 0.7 for adolescent boy (13-18 years old)
ht Height in centimeters
Pcr Plasma concentration of creatinine in mg/dl
When timed urine collection is not possible, simply Haycock-Schwartz formula is
the best, easiest and cheapest way to assess GFR.
2. DTPA scan: Can assess split functions of both kidneys

Page | 217

Control of renal hemodynamics occurs through the following mechanisms:
1. Renin-Angiotensin-Aldosterone System (RAAS) primed by Juxtaglomerular
apparatus (JGA): composed of two cell types, macula densa cells(modified
distal tubular cells) and juxtaglomerular cells, located at the junction of the
afferent and efferent arterioles
- Low renal vascular flow

- Low sodium delivery at the
macula densa cells
Stimulate release of Renin from the

juxta glomerular cells
Renin converts angiotensinogen

released by the liver to Angiotensin I
Angiotensin I is converted to
Angiotensin II in the lungs by
Angiotensin Converting Enzyme (ACE)
Angiotensin II
- A very potent systemic vasoconstrictor
- Stimulates release of Aldosterone by supra renal gland
Increase renal blood flow
Aldosterone is secreted by supra renal gland zona

glomeruloza. It enhances distal tubular salt and water
retention in exchange with H+ or K+

Page | 218
2. Intra renal prostaglandins

PGE2 and prostacyclin [PGI2] are vasodilators
They counteract primarily angiotensin II–mediated vasoconstriction
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin will block
prostaglandin synthesis and restrict the compensatory renal vasodilation
3. Atrial natriuretic peptide (ANP)
Is released from the right cardiac atrial myocytes in response to stretch (at
high blood volume)
ANP dilates the afferent arteriole, and constricts the efferent arteriole,
increasing glomerular capillaries hydrostatic pressure, and thus, GFR.
The enhanced flow increases sodium and water excretion, reducing blood
volume.
Blood filtrate barrier ultrastructure

1. Epithelial cells (Podocytes)
2. Glomerular basement membrane
3. Endothelial cells

Page | 219
Hematuria
Definition
Macroscopic (Gross) hematuria: Blood in the urine visible to the naked eye
Microscopic hematuria:
- More than 5 red blood cells (RBCs) per high-power field on freshly
voided and centrifuged urine
- Isolated asymptomatic microscopic hematuria is found in up to 4% of
healthy children.
Presentation
Episode of macroscopic hematuria (causes alarm to child/family).
Incidental finding of microscopic hematuria.
Family screening and routine urinalysis.
Other causes of ‘red urine’
The following can usually be distinguished from hematuria by taking a
careful history, and with urine dipstick testing and microscopy:
A. Pathologic
- Hemoglobinuria
- Myoglobinuria
B. Non pathologic
- Foods coloring (e.g. beetroot).
- Drugs (e.g. rifampicin).
- Urate crystals (in young infants, usually ‘pink’ nappies).
- External source (e.g. menstrual blood losses).
- Fictitious: consider if no cause found
Causes of haematuria
A. Glomerular
1. Immunologic injury :Glomerulonephritis (GN)
2. Structural disorder (Alport syndrome, thin basement membrane disease)
3. Toxin-mediated injury (HUS)
B. Extra Glomerular
R Tubulo interstitial/Parenchymal
a. Inflammation (interstitial nephritis, pyelonephritis)
b. Vascular (sickle cell trait/disease, renal vein thrombosis)
c. Structural (cyst rupture, Wilms tumor, urinary tract obstruction, trauma)
R Lower urinary tract
a. Inflammation (cystitis, hemorrhagic cystitis, urethritis)
b. Injury (trauma, kidney stone)
c. Hypercalciuria
(Essential Nelson)

Page | 220
Glomerulonephritis (GN)
Definition: Group of diseases with acute glomerular injury. Initiated in most
cases by immunologic mechanism. With variable presentation of:
- Acute kidney injury (AKI) (oliguria, uremia, elevated creatinine)
- Hematuria
- Hypertension
- Peripheral edema
- Proteinuria
Classification
With low serum complement (C3,CH50) With normal serum complement

Renal disease Renal disease
Acute post infectious GN (> 90%) IgA nephropathy
- Post streptococcal GN
- Other infections: e.g. staph,
pneumococci, HBV, ….
Membranoproliferative GN type 1
Systemic disease Systemic disease
Chronic Post infectious GN: Vasculitis
- Infected shunt Henoch-Schönlein purpura
- Infective endocarditis Goodpasture’s syndrome
Lupus nephritis
Acute Post Streptococcal Glomerulonephritis (APSGN)

Definition and Etiology
x Acute Nephritic syndrome which follow infection with nephritogenic strain of
group A-E hemolytic streptococci causing throat infection or skin infection
x Streptococcal pyogenic exotoxin (SPEB) mimic glomerular basement membrane
Post pharyngitis GN Post skin infection GN

Stains of strept. - Serotypes :1,3, 4,12,18 - Serotypes :2,49,55,57
Season - Cold(winter) - Tropical(summer)
Sex incidence ( M: F ratio) - 2:1 - 1:1
Susceptible age - School age - Pre School age
Latent period - 1-2 weeks - 2-6 weeks; typically in
child with eczema
Serology:
ASO titer - Elevated - May be absent
Anti DNAse B - Elevated - Elevated

Page | 221

Pathogenesis
Streptococcal infection Latent- period Antibodies
p
Antigen + Antibody + Complement (C3) immune complexes
p
Deposited in glomerular basement membrane (subepithelial humps)
p
Acute inflammation
Proliferation of mesangeal and Glomerular endothelial damage
endothelial cells. p
p Hematuria ± proteinuria
Glomerular capillaries narrowing.
p
Impaired Glomerular blood flow
p Glomerular filtration rate. + + Juxta-glomerular apparatus (JGA)

p
Fluid retention + + Renin- Angiotensin Aldosteron system
p p
Oliguria Hypervolemia Hypertension
p
Edema

Page | 222

Clinical picture
Mean age: 7 years.
History of a preceding skin or throat infection 1-3 weeks ago may be obtained
Gradual or sudden onset of:
1. Hematuria : - The 1st presenting feature
- Painless
- Cola colored (smoky) urine or bloody
with gross hematuria
- Urine rarely appears normal with
microscopic hematuria
2. Edema : - 2nd presenting feature

- Mild, morning periorbital puffiness & pretibial edema
- Mainly due to reduced GFR and hypervolemia
3. Oliguria : - Urine output (UOP) < 1 ml/kg/hr or < 400 ml/m2/day
- Some others have anuria or rarely normal urine volume
4. Hypertension : - Transient ; mostly resolves by the end of 1st week
- Mild to severe
- Seen in 60-70% at any time in the acute phase
- Principally due to salt and water retention
5. Nonspecific: - Headache, anorexia, vomiting, abdominal pain, mild fever.
6. Some cases are asymptomatic and discovered accidentally on routine
urinalysis
Complications: May be the presenting event
1. Heart Failure and acute pulmonary edema
Due to hypertension or hypervolemia
Clinically
R Respiratory distress and orthopnea
R Tachycardia, tachypnea, tender liver
R Acute pulmonary edema
- Severe respiratory distress
- Cyanosis
- Wide spread crepitations
2. Hypertensive encephalopathy
Due to acute hySHUWHQVLRQĺcerebral edema ± hemorrhages
Clinically
R Severe headache
R Blurred vision
R Vomiting ĺFRQYXOVLRQVĺFRPD

Page | 223
3. Acute renal failure (ARF)

Due to rapidly progressive (crescentic) GN
Usually transient
Clinically
R Marked oliguria or anuria
R Acidotic breathing
R Uremic encephalopathy
Investigations
A. For diagnosis ĺUrinalysis
Color: Smoky or gross hematuria.
Specific gravity: High
Proteinuria: Usually ‫ޒ‬1gm/dl (nephrotic range is seen in 10-20%)
Microscopy: Dysmorphic RBCs / RBCs casts which is pathognomonic to
glomerular bleeding
Timed urine output collection or 24 hours collection can prove
oliguria/anuria
B. For effect
(OHFWURO\WHVĺPD\EHK\SHUNDOHPLD GLOXWLRQDOK\SRQDWUHPLD
Renal function WHVWVĺ may be impaired.
$QHPLDĺGXHWRKHPodilution
C. For etiology
x Low complement component C3 (Normal C4)
x Evidence of recent streptococcal infection:-
- Throat or skin lesion swab culture
- Anti- streptolysin O (ASO) titer ĺ!WRGGXQLWPD\EH
negative after skin infection. ( ASO titer is raised in up to 20% of
healthy children)
- Anti Deoxyribonuclase B titre (Anti- DNase B).
x Renal biopsy is indicated for :
a. In acute phase:
Nephrotic syndrome ( nephritic nephrosis)
Rapidly rising creatinine suggesting rapidly progressive
glomerulonephritis
b. For prognosis in atypical course
Abnormal creatinine at 6 weeks
Low C3 > 3 months
Proteinuria > 6 months

Page | 224
Light microscopy
Glomerulus is
- Hypercellular
- Capillary loops are
poorly defined.
- Massive influx of
neutrophils
Immunofluorescence microscopy
Reveals:
“lumpy-bumpy” deposits of
immunoglobulin and
complement on the glomerular
basement membrane (GBM)
and in the mesangium
Electron microscopy
Reveals:
Glomerular subepithelial
cone-shaped electron-dense
deposits, referred to as
“humps.”

Page | 225
Course
- Nephritis manifestations usually resolve by 2-3 weeks
- C3 normalize by 6-8 weeks of onset
- Abnormal urinalysis improve within 4-8 weeks of onset
- Microscopic hematuria may persist for 1-2 years with no long term relevance
Differential diagnosis:
From other causes of Hematuria (see later)
Treatment
1. Bed rest as needed by the patient or with complications
2. Course of penicillin for 10 days is necessary to prevent spread to contacts
but will not help the nephritis.
3. Diet
Assess fluid balance
Fluid restriction:
- In oligo-anuria to avoid hypervolemia.
- Intake = urine output plus insensible loss (200-400ml/m2/d or 20-40
ml/kg/day) plus any additional losses (vomitus or diarrhea)
- Given as 0.45% saline /2.5 % dextrose or 0.45% saline /5-10 %
dextrose in infants
Salt restriction
Potassium and prRWHLQUHVWULFWLRQĺRQO\ZLWKUHQDOIDLOXUH
Provide calories (reduce catabolism) by giving enteral Maxijul 10-
20% via naso-gastric tube
4. Hypertension (Elevated blood pressure):
Mild to moderate hypertension Severe hypertension
- Fluid restriction - Furosemide
- Furosemide 2-5 mg/kg IV - Na nitroprusside (infusion)
- ACE inhibitor e.g Captopril - Hydralazine
- Angiotensin Receptor Blockers - Diazoxide (i.v. push).
- Nifidipine or Amelodipine.
5. Treat Complications (Failures):
Heart failure: Treatment depends on the underlying cause:
R Hypertensive KHDUWIDLOXUHĺWUHDWK\SHUWHQVLRQ
R Hypervolemic KHDUWIDLOXUHĺGLXUHWLFVGLDO\VLV
Acute renal failure:
R Conservative treatment with or without peritoneal
dialysis(see later)
R Cresentic nephritis on biopsy may benefit from
immunosuppression e.g. pulsed IV methyleprednisolone
(Oxford Pediatric Nephrology)

Page | 226
6. Discharge from hospital (Go home) if there is:

R No gross hematuria
R Normal renal functions
R No or controlled hypertension
Prognosis
- Over 95% of post streptococcal glomerulonephritis recover completely
- Less than 5% go into rapidly progressive glomerulonephritis may end in
chronic renal failure.
- Mortality is due to heart failure, hypertension and renal failure
- Recurrence is extremely rare

Page | 227
IgA Nephropathy (Berger Nephropathy)

IgA nephropathy is an immune complex disease
It is characterized by a predominance of IgA within mesangial deposits of the
glomerulus in the absence of systemic diseases such as systemic lupus
erythematosus or Henoch-Schönlein purpura.
The most common chronic glomerular disease worldwide.
Clinical
Recurrent gross (macroscopic )hematuria*
- Commonest presentation
- Occur 1-2 days following upper respiratory tract infection
Asymptomatic microscopic hematuria u proteinuria.
Nephritic syndrome
Nephrotic syndrome
Nephritic-nephrotic syndrome.
Progressive renal dysfunction in adulthood.
Diagnosis
Normal serum levels of C3
Serum IgA levels have no diagnostic value
Renal biopsy : mesangeal deposits of IgA
Treatment
There is no accepted treatment regimen; most are controversial.
A. Microscopic hematuria /recurrent gross hematuria:
- Of no clinical significance
- Tonsillectomy is advised by some investigators
- Some reports suggest vit E
B. Proteinuria & hypertension
- ACE inhibitors & angiotensin II receptor antagonists
C. Patients with adverse risk factors:
Treat proteinuria and hypertension
Immunosuppression including: steroids azathioprine, cyclophosphamide,
mycophenolate mofenil (MMF)
Fish oil (contains anti-inflammatory omega-3 fatty acids)
- May decrease the rate of renal progression in patients with
progressive disease
- Preparation : Omacor capsule and Maxepa syrup
- Main side effect is halitosis and none adherence
D. Successful renal transplantation
Recur in only 15–30% of patients

Page | 228
Rapidly Progressive (Crescentic) Glomerulonpehritis

Crescents in the majority of glomeruli progress rapidly to end-stage renal failure.
Causes
1- Immune complex glomerulonephritis:
- Post-streptococcal glomerulonephritis.
- Henoch Shönlein purpura
- IgA nephropathy
- Lupus nephritis
- Membranoproliferative GN (MPGN)
2- Anti Glomerular Basement Membrane GN
(Good Pasture Syndrome):
Pulmonary hemorrhage and glomerulonephritis associated with antibodies
against lung and against glomerular basement membrane (anti-GBM)
Hemoptysis: is usually the presenting complaint (that may lead to death).
Hematuria, proteinuria, and progressive renal failure
Anti-GBM antibodies confirm the diagnosis
3- Idiopathic.
4- ANCA mediated glomerulonephritis (Wegner granulomatosis)
Pathology
Characteristic Crescents inside Bowman capsule composed of:
- Proliferating epithelial cells
- Fibrin
- Basement membrane like material
- Idiopathic form: absent deposits; only crescents.
Clinical picture:
Suspected in acute nephritic episode leading to acute renal failure
Diagnosis
1- Serologic studies e.g. C3, anti-Dnase-B,….
2- Renal biopsy
Prognosis and Treatment

Spontaneous recovery may occur with post streptococcal type
Treatment options (choice is cause related):
- Pulsed methyle prednisolone / oral prednisone
- Plasma exchange
- Cyclophosphamide
- Biological agents: Rituximab, Anti-TNF therapy
- Supportive care of ARF e.g. Dialysis

Page | 229
Hemolytic Uremic Syndrome (HUS)

Definition
One of the most common causes of community-acquired acute kidney
failure in young children
It is characterized by the triad of : Microangiopathic hemolytic anemia
thrombocytopenia, and renal insufficiency
Causes
1. Infection induced
Often preceded by acute bloody diarrhea (Typical HUS) caused by:
- Vero toxin -producing E. coli (Enterohemorrhagic E coli); mainly
O157:H7 (Europe , America)
- Shiga toxin producing Shigella dysenteriae type 1 (Asia-Africa)
9 Transmitted by undercooked meat or unpasteurized milk
9 Epidemics have followed ingestion of undercooked, contaminated
hamburger at fast food restaurants
Neuraminidase (T antigen) -producing Strept.pneumonia is a rare cause.
2. Other less common causes
Genetic (inherited HUS)
- Defective Von Willebrand factor–cleaving protease (ADAMTS 13)
- Defective Complement factor H, I, or B
- Defects in vitamin B12 metabolism
Secondary HUS
- Antiphospholipid syndrome
- Systemic lupus.
- Drugs (Cyclosporin ,chemotherapy)
- Bone marrow transplantation
Pathogenesis
TR[LQV EDFWHULDO RWKHUV ĺ/HXFRF\WHVĺn tumor necrosis factor &
interleukin 2
n O2 Free radicles. n Procoagulants

p
endothelial damage
Intra vascular thrombi
Damaged circulating RBCs & platelets Glomerular obstruction
Micro angiopathic hemolytic Anemia Acute renal failure

/ Thrombocytopenia. /Hematuria

Page | 230

Clinical picture
Common age: most common in preschool and school-aged children
Acute diarrhea (often bloody) or respiratory infection is followed few days
later by :
- Acute hemolysis ĺ Acute pallor, jaundice and purpura
- Acute renal failure ĺ Oliguria, edema, hypertension, acidotic
breathing.
- Hematuria and may be hemoglobinuria
Genetic forms
- Onset is insidious
- Triggered by a variety of illnesses, including mild, nonspecific
gastroenteritis or respiratory tract infections
Complications:
- Acute renal failure
- Acute heart failure (hypervolemia, hypertension, anemia)
- $FXWHQHXURORJLFG\VIXQFWLRQHQFHSKDORSDWK\LQ
Workup
For diagnosis
For ARF - High creatinine and blood urea nitrogen
- High potassium
- Metabolic DFLGRVLV ĻS+Ļ3D&22Ļ+&23)
For MAHA - Anemia
- Reticulocytosis
- Negative Coombs test (except pneumococci-induced HUS)
- Blood Film: IUDJPHQWHG5%&V +HOPHW¶VFHOOV, shistocytes)
For bleeding - Thrombocytopenia counts usually 20,000-100,000/mm3.
- &RDJXODWLRQSURILOHĺ1RUPDO (unlike DIC)
Urinalysis - Hematuria and may be hemoglobinuria
For etiology
- History of diarrheal prodrome or pneumococcal infection
- If history is negative, consider evaluation for genetic causes
- Stool culture is often negative in diarrhea-associated HUS (even, risk of
developing HUS with intestinal E.Coli 0157:H7 is only 10%)
1. From other causes of intrinsic renal failure
2. From other causes of microangiopathic hemolytic anemia: e.g.
- Bilateral renal vein thrombosis (Marked renal enlargement , Doppler)
- DIC

Page | 231

Treatment
i. Prevention
- Adequate cooking of meat (especially Hamburger)
- Isolation of cases to avoid cross infection with E.coli
ii. Curative
Rules of management
- Early recognition of the disease
- Monitoring for potential complications
- Meticulous supportive care
ARF
- Meticulous fluid and electrolyte management
- Early dialysis or hemofiltration is usually indicated
- Treatment as for intrinsic acute renal failure
Packed RBCs
- May be repeated in active phase as hemolysis take up to 2 weeks
- For hemoglobin ‫ޒ‬JUDPGO
- In pneumococci-associated HUS use washed red cells (remove
residual plasma containing IgM directed against T antigen )
Platelets
- Should generally not be administered(consumed by the active
coagulation and can theoretically worsen the clinical course)
- Considered only if elective surgery is indicated or with ICH
Others
- Antibiotics can result in increased toxin release, potentially
exacerbating the disease. It is not recommended except for any
underlying pneumococcal infection
- Plasma infusion or plasmapheresis is considered for serious CNS
involvement and in atypical HUS
- Eculizumab; Mono clonal antibody against C5 is promising in
atypical (genetic) HUS, even in patients resistant to plasma therapy.
Prognosis
9 Course is unpredictable
9 HUS can be relatively mild or can progress to a severe, and even fatal,
multisystem disease
9 More than 50% require dialysis ; 5% remain dependent on dialysis, and
up to 20-30% are left with some level of chronic renal insufficiency.
9 Patients who have recovered completely, with no residual urinary
abnormalities after a year, are unlikely to manifest long-term sequelae

Page | 232
Alport Syndrome
Definition
Multisystem disorder : Hereditary nephritis, sensineural deafness and
often eye abnormalities
Classical Alport syndrome is due to mutations in Į chain of type IV
collagen (COL4); a major component of basement membranes.
Genetics
Mainly X- Linked disease (85%) caused by a mutation in the COL4 Į 5
gene; some are associated with diffuse leiomyomatosis.
Autosomal recessive or autosomal dominant form (less common).
Clinical manifestations
L5HQDOPDQLIHVWDWLRQV
1. Hematuria
- Affects 100 % of males and 95% carrier females
- Asymptomatic microscopic hematuria, which may be intermittent
- Recurrent gross hematuria*
2. Proteinuria
- Common in males; may be absent, mild, or intermittent in
females.
- Progressive by the second decade of life
Renal pathology
Light : non specific
Electron microscopy
Reveals:
- Diffuse thickening, thinning, splitting of the basement
membranes of the glomeruli &tubules
- Lamellation of the basement membrane (basket wave pattern)

Page | 233
Prognosis
ESRD occurs before age 30 years in approximately 75% of hemizygotes
with X-linked AS.
Risk factors for progression
- Gross hematuria during childhood.
- Nephrotic syndrome.

LL([WUD5HQDOPDQLIHVWDWLRQV
Hearing deficits
Affects 90% of males with X-linked AS, less common in cases with
autosomal recessive AS, and only 10% of heterozygous females with X-
linked AS.
- Bilateral sensorineural hearing loss

(Never congenital in onset)
- Starts for the high-frequency range
but progresses to involve
conversational speech
- Hearing aids are eventual.
Ocular abnormalities
Mainly affects patients with X-linked
- Anterior lenticonus (extrusion of

the central portion of the lens into
the anterior chamber) is
pathognomonic
- Corneal erosions.
- Macular flecks.
Rarely
Leiomyomatosis of the
esophagus, tracheobronchial
tree and female genitalia
Platelet abnormalities
Endoscopic image of eosophageal submucosal

leiomyoma and endoscopic US

Page | 234
Diagnosis
Requirements
- Family history
- Screening urinalysis of first-degree relatives
- Audiogram
- Ophthalmology exam
Diagnositic
Hematuria with anterior lenticonus is pathognomonic
Hematuria with at least two of the following characteristics:
- Sensorineural deafness
- GBM thickening and thinning (by EM)
- Macular flecks
- Recurrent corneal erosions
Basement membrane collagen studies.
Note
- Mutation screening or linkage analysis is not clinical use.
- Prenatal diagnosis is available for familial sex linked disease.
Treatment
9 No specific therapy for Alport syndrome.
9 Angiotensin-converting enzyme inhibitors may slow the rate of
renal progression.
9 Supportive treatment for renal failure (conservative, dialysis ,
kidney transplantation); 5% of renal transplant recipients develop
anti-GBM nephritis.

Page | 235

Approach to Hematuria
We should exclude other causes of red urine without RBCs by urine analysis
(Dipstick) which includes:-
A. Heme positive
Hemoglobinuria in case of acute hemolytic anemia.
- CBC shows fragmented RBCs & reticulocytosis
- Hemoglobin in urine
Myoglobinuria in case of rhabdomyolysis (myositis, crush )
- High serum creatine kinase.
B. Heme negative - Foods e.g. Beet roots, black berries.
- Drugs e.g. Rifamipicin, Desferal, Nitrofurantoin.
- Urate crystals (red diaper).
History
Glomerulonephritis: sore throat/rashes/body swelling
UTI: fever/frequency/dysuria.
Renal stones: colicky abdominal pain/family history.
Coagulopathy: easy bruising.
Trauma
Family history: hematuria, deafness (Alport’s), sickle cell disease.
Examination
Blood Pressure (use age,sex and height appropriate blood pressure centiles)
Abdomen: palpable masses (polycystic kidneys, tumors, hydronephrosis).
Skin: rashes.
Joints: pain/swelling.
Investigations
x It is important to identify serious, treatable, and progressive conditions.
x During an acute illness, exclude UTI by urine culture.
x Asymptomatic or ‘benign haematuria’ in children without growth failure,
hypertension, oedema, proteinuria, urinary casts, or renal impairment is a
frequent finding.
1. Localize hematuria
Glomerular Extra glomerular
Acute nephritic syndrome Present Absent
Color Cola or tea colored Bright red
Clots Absent May present
RBCS Shape Dysmorphic (distorted) Normal
RBCS casts Present Absent
Proteinuria > 30 mg / dL. < 30 mg / dL.

Page | 236
Typical appearance of RBCs in glomerular Typical appearance in non-glomerular

hematuria: RBCs are small and vary in hematuria: RBCs are uniform in size and
size, shape, and hemoglobin content shape, along with numerous polymorphs
(Consensus Statement on Evaluation of Hematuria, Indian Pediatrics 2006)
2. For Glomerular hemturia:

Hematology
- CBC with differential
Chemistry
- Electrolytes, Ca
- BUN/ Creatinine /Creatinine clearance
- Serum protein/Albumin /Cholesterol
- Urine protein
Immunology
- C3/C4
- ASO/Anti-DNase B
- ANA
- Antineutrophil antibody
Reduced C3 in - Post infectious glomerulonephritis

- Systemic lupus nephritis (and low C4)
- Nephritis with chronic infection
- Membrano proliferative glomerulonephritis
3. Renal Biopsy
- Unexplained persistent or recurrent gross hematuria
- Lupus nephritis
- Glomerulonephritis with: o nephritic nephrosis
o Absent low C3
- Unexplained acute renal

Page | 237
4. For extra glomerular hematuria

Step 1
- Urine culture
Step 2
- Urine calcium/creatinine ratio
- Sickle prep (African American)
- Renal/bladder ultrasound
Step 3
- Urinalysis: siblings, parents
- Serum electrolytes, Cr, Ca
- If crystalluria, urolithiasis, or nephrocalcinosis: 24-hour urine for Ca,
creatinine, uric acid, oxalate
- If hydronephrosis/pyelocaliectasis: Cystogram, renal scan
Treatment
If obvious cause (e.g. UTI), treat.
If complex diagnosis (impaired renal function, proteinuria, or family
history) refer to paediatric nephrology unit.
If no cause found and normal renal function, BP, and no proteinuria,
monitor until resolves.
If no resolution after 6mths or change in any of above parameters refer to
paediatric nephrology unit.

Page | 238

Proteinuria
Normal values
Most of the proteins filtered by the glomeruli are reabsorbed by the proximal
convoluted tubules.
The normal daily urinary protein loss is < 4 mg/m2/hr or < 150 mg/24hr.
Detection
1. Urine dipstick analysis (Albustix)
Less sensitive; affected by urine specific gravity and pH.
Primarily detects albuminuria ; less sensitive for other forms of proteinuria
Reported as:
- Negative
- Trace (10-20mg/dl)
- 1+ (30 mg/dl)
- 2+ (100mg/dl)
- 3+ (300 mg/dl)
- 4+ (1000–2000mg/dl)
2. Timed (24-hr) urine collections
Quantitative for proteinuria (not practical)
Normal value < 4 mg/m2/hr.
Abnormal 4 – 40mg/m2/hr.
Nephrotic range > 40 mg/m2/hr or > 50 mg/kg
3. Spot urine protein: creatinine ratio (UPr: UCr)
Quantitative for proteinuria and more practical timed urine collections
Use early morning urine sample
Normal value < 0.5 (<LQFKLOGUHQ yr)
Nephrotic-range proteinuria > 2
Causes of proteinuria
i. Transient proteinuria (Never exceed 2+):
- Postural or orthostatic : Proteinuria in upright posture only.
- Non postural: - Fever, vigorous exercise, seizures
ii. Persistent proteinuria
Tubular Glomerular
Due to Decreased reabsorption of Increased glomorular basement
filtered proteins. membrane (GBM) permeability.
Level Usually < 1gm/24 hours Can exceed 1gm/24 hours
Type Low molecular weight proteins Low and high molecular weight
proteins
Albuminuria Absent. Present.
Associations Other proximal tubular defects Edema.
e.g glucosuria, phosphaturia May be hypertension, hematuria.
Causes Fanconi syndromes - Damage to GMB, e.g. GN
(Cystinosis, Lignac,…… …) - Dysfunction of GBM e.g.:
Minimal change nephrotic syn.

Page | 239
Nephrotic Syndrome
Definition: Clinico-laboratory condition characterized by:-
Nephrotic range proteinuria defined as urinary proteins > 40 mg/m2/hr or
a first morning protein : creatinine ratio of > 2-3 : 1
Hypoalbuminemia
Generalized edema
Hyperlipidemia
Incidence: 15 times commoner in children than adults
Causes of Nephrotic Syndrome
1. Idiopathic (? Lymphocyte dysfunction o altered GBM permeability)
R 90% of cases
R Histologic types
- Minimal change disease (85%)
- Focal segmental glomerulosclerosis
- Membranous nephropathy
2. Genetic nephrotic syndrome
- Finnish-type congenital nephrotic syndrome (absence of nephrin)
- Focal segmental glomerulosclerosis (podocin, actinin mutations)
- Diffuse mesangial sclerosis (laminin mutations)
- Denys-Drash syndrome (mutations in WT1 transcription factor)
3. Secondary nephrotic syndrome
Due to Examples
Glomerulonephritis with - Systemic lupus nephritis
heavy proteinuria - Henoch Schonlein purpura
Infection - Hepatitis B, C
- HIV-1
- Malaria
- Syphilis
- Toxoplasmosis
Allergy - Serum sickness
- Bee sting
Drugs - Penicillamine
- Gold salts
- Interferon
- Nonsteroidal anti-inflammatory drugs
Diseases - Sickle cell disease
- Amyliodosis
- Thrombosis of renal veins
Tumors - Hodgkin lymphoma /Leukemia

Page | 240

Histological classification
1. Minimal change nephrotic syndrome (MCNS)
Light microscopy and LPPXQRIORUHVFHQFHĺQRUPDO
(OHFWURQPLFURVFRS\ĺORVs
of podocytes foot processes.
Proteinuria is selective
Steroid responsive in > 95%.
In prolonged cases as in relapses or resistance WRWUHDWPHQWĺPRUH
notable changes are seen as focal glomerulosclerosis
Electron microscopy photo of a normal Electron microscopy photo of a glomerulus in

glomerulus with epithelial cells with MCNS showing diffuse effacement of epithelial
normal loose foot processes foot processes
2. Focal segmental glomerulosclerosis (FSGS):

Light and electron microscopy ĺSegmental sclerosis
ĺFocal sclerosis
Steroid responsive in < 20%.
3. Mesangeal proliferative glomerulonephritis

Light and HOHFWURQPLFURVFRS\ĺLQFUHDVHPHVDQJHDOFHOOV PDWUL[
Steroid responsive in < 50%.
4. Membranous
Light & electron microscopy:
- Uniform thickening of glomerular basement membrane
- Focal sclerosis as the disease progress

Page | 241
Idiopathic Nephrotic Syndrome
Pathogenesis
1. Proteinuria
* Due to increased glomerular basement membrane (GBM) permeability
(Due to defect in size or altered negative charges of GBM barriers)
Proteinuria is either
- Selective = escape of low molecular - Non selective = escape of both

weight proteins as albumin. low & high molecular weight
proteins
2. Hypoproteinemia
Decreased WRWDOVHUXPSURWHLQVĺbasically hypoalbuminemia
3. Hyperlipidemia 4. Generalized oedema
Mainly hypercholestrolemia. 'XHWRĻSODVPDRVPRWLc pressure

Due to ĻSURWHLQV DOEXPLQ
Ļ
fluid shift to interstitial tissue
Hypoproteinaemia ĻOLSRSURWHLQ
Lipase (mainly in lax & gravity dependent)
Ļ Ļ Ļ
Stimulate Ļ/LSLG ĻLQWUDYDVFXODUYROXPH
the liver catabolism
Ļ
n$'+ĻRenal blood flow
ĹProtein synthesis Ļ
including lipoproteins ++ JGA
Ļ
n Aldosterone
Water UHWHQWLRQĻ
Salt and water retention
More oedema.

Page | 242

Clinical picture
9 Peak age in MCNS =2-7 years/ Boys: Girls 2:1
9 The initial episode and relapses may follow viral upper respiratory tract
infection.
1. Generalized edema
Start as morning periorbital puffiness then progress to involve lower
limbs,genitalia and abdominal wall with stretched skin and skin breaks
Oedema is very soft, pitting,
Ascites and pleural effusion are very commonĺPD\EHUHVSLUDWRU\
distress.
:LWKGHYHORSLQJHGHPDDQGLQFUHDVLQJZHLJKWĺXULQHYROXPHLV
declining
2. *DVWURLQWHVWLQDOPXFRVDORHGHPDĺDQRUH[LDDEGRPLQDOSDLQ GLDUUKHD
3. Hypertension may occur in only 5-10%.
Complications
1. Hypovolemia
Precipitated by Presentation
- Sepsis - Abdominal pain
- Diarrhea - Hypotension
- Use of diuretics - Poor perfusion
- Hemoconcetration
2. Acute renal failure (Nephrotic crisis)

Precipitated by
- 6HYHUHK\SRYROHPLDĺpp renal blood flow (pre renal failure).
- Renal vein thrombosis.
- Sepsis

Page | 243
3. Intra vascular thrombosis

Precipitated by
- +\SRYROHPLDĺKHPRFRQFHWUDWLRQĺVOXJJLVKFLUFXODWLRQ
- Increased platelet adhesiveness and certain coagulation factors.
- Decreased natural anti-coagulants e.g. Anti thormbin III and protein C.
Common sites
Cerebral cortical veins Renal veins Deep venous thrombosis
4. Infections
Precipitated by
- Loss of immunoglobulins and complement factor B
- Edema or ascites acting as a potential culture medium
- Immuno suppressive therapies
Common infections: basically by capsulated bacteria and viruses
- Spontaneous bacterial peritonitis (Strept. pneumoniae, E.Coli)
9 Child looks ill, feverish with persistent abdominal pain
9 Prompt evaluation (including cultures of blood and peritoneal
fluid), and early initiation of antibiotic therapy are critical.
- Others: urinary tract infections (E.coli) ,pneumonia (H. influenza),
cellulitis (Staph aureus), and sepsis
5. Relapse
Recurrence of significant proteinuria ;urine Albustix ++ or more for 3
consecutive days
Frequent Relapsing Nephrotic Syndrome (FRNS): Relapses 4 or more
within 12 months period.
Steroid Dependent Nephrotic Syndrome (SDNS): nephrotic syndrome that
relapses during steroid tapering or immediate after steroid withdrawal.
6. Complications in Resistant and FRNS
Protein depletion: muscle wasting, osteoporosis, short stature
&KURQLFUHQDOIDLOXUHĺLQQRQ- MCNS
Drugs complications: See later

Page | 244
Investigations
1. For diagnosis
A. Urine analysis
Heavy Proteinura:
)LUVWPRUQLQJSURWHLQௗFUHDWLQLQHUDWLRRI!-3:ௗ (Timed urine
protein > 40 mg/m2/hr)
- Color: Yellowish, frothy
- Specific gravity: High
- Waxy (lipoid) & hyaline casts.
- Microscopic hematuria in about 10% of MCNS.
B. Biochemical
Low serum albumin < 2.5 gm/dl (normal: 3.5 - 4.5 gm/dl),
Low total proteins < 4.5 gm/dl. (normal :6.5 - 8 gm/dl)
Increased serum cholesterol > 220 mg/dl
- Complement C3 and C4 levels (Normal in MCNS)
2. Workup before starting therapy

CBC.
Urine microscopy and culture as there is an increased rate of UTI.
Infectious disease workup including
- PPD (Mantoux) skin test and chest X-ray in TB endemic areas.
- Varicella zoster serology to determine immune status.
- Hepatitis B and C serology.
Lupus antibody serology (ANA, extractable nuclear antibodies (ENA),
and ds-DNA) in older children, and those with atypical presenting
features
3. Renal biopsy
- Not indicated if MCNS is suggested.
- Indications.
Before treatment After treatment

- Age < 1 or >12 years. - Steroid resistance.
- Gross hematuria. - Frequent relapsing
- Renal failure
- Low C3

Page | 245
1. Form other causes of generalized edema (See Clinical)
2. From causes of secondary nephrotic syndrome:
A diagnosis other than MCNS should be considered in
Children <1 yr of age
A positive family history of nephrotic syndrome
Presence of :
- Extrarenal findings (e.g., arthritis, rash, anemia)
- Hypertension or pulmonary edema
- Acute or chronic renal insufficiency
- Gross hematuria
Treatment of Nephrotic Syndrome

Supportive care
1. Fluid balance, hypovolemia, and blood pressure
Mild peripheral edema:
- Do not require fluid restriction
Significant edema
- Mild fluid restriction (70 % of maintenance requirements)
- A low salt diet control thirst and minimizes edema
Regular assessment of temperature, weight, BP, hydration state
2. Avoid infections
Avoid contact with infectious patients
Broad spectrum Antibiotics for any current infections pending bacterial
cultures
Nonimmune child, if exposed to Varicella, should receive varicella-
zoster immunoglobulin dose within 4days after significant exposure.
Edematous child should receive prophylactic penicillin V 12.5mg/kg bd
Vaccines :
9 Routine vaccines should be given during remission
9 Live vaccines should only be administered when the child is off all
immunosuppressive therapy (1 month following discontinuation of
steroids and 3-6 months following discontinuation of cyclosporine
and cyclophosphamide).
9 Other recommended vaccines: Pneumococcal(both types) , H.
influenza vaccines and annual influenza/H1N1 vaccine

Page | 246

3. Avoid thrombosis
Low dose aspirin
Treat hypovolemia either by:
- Plasma 20 ml /kg or
- 4.5 % albumin solution 10 – 20ml/kg
- Diuretics should be stopped or avoided in this setting
4. Salt free albumin
ȋ Ȍ

- ͳȀȋͷȀʹͲΨȌ
- Ͷ
- ͳȂʹȀ

Specific therapy
Induction of remission by Prednisone 60 mg/m2/d or 2 mg/kg/d (maximum
dose 80mg) for 4 weeks in a single daily dose
p
Response
Proteinuria (2+ or greater) persist:

Urine albustix negative or trace
9 After 8 weeks of steroids Or
for 3 consecutive days (timed
9 After 4 weeks of steroids
urine protein < 4mg/m2/hr)
followed by 3 methyl
Serum albumin gm/dl.
prednisolone pulses.
In absence of infection or non-
adherence to medication
Remission of
nephrotic syndrome
Steroid Responsive Nephrotic Syndrome Steroid Resistant Nephrotic

Syndrome
1. Steroid Responsive Nephrotic Syndrome:
After the initial 4 weeks induction:
- Use alternate day prednisone 40 mg/m2 as single morning dose for 4 weeks
- Followed by gradual withdrawal over 4 months with monitoring for proteinuria

Page | 247

Suggested plan:
40 mg/m2 íPJNJ 4KRXUVIRUZHHNVWKHQ
20 mg/m2 íPJNJ 4KRXUVIRUZHHNVWKHQ
10–15 mg/m2 (0.5 mg/kg) Q48 hours for 4 weeks, then
5–7.5 mg/m2 (0.25 mg/kg) Q48 hours for 2 months
(Manual Of Pediatric Nephrology)

Outcomes
No rHODSVHV ĺ2EVHUYH
5HODSVH!PRQWKVDIWHUVWHURLGZLWKGUDZDOĺ5HWUHDWPHQWDVDERYH
Relapse while on alternate day steroid therapy or < 28 days after steroid
withdrawal are termed steroid dependent nephrotic syndrome ; 60%
* Re induction followed by alternate day steriods

* Then to minimize relapse rate try the following:
1- Prolong alternate day steroid therapy for up to12-18 months
2- Steroid sparing therapies:
Levamizole 2.5 mg/kg Every 48H for 12 months
Cyclophosphamide 2 mg/kg/day for 12 week
Cyclosporine (CSA) 5íPJNJGD\
Mycophenolate Mofitel (MMF) 600–1200mg/m2/day 12 months
Tacrolimus(Prograf) íNJGD\RUDWOHDVWPRQWKV
Rituximab Every íPRQWKVPJP2 per
infusion
2. Steroid resistant nephrotic syndrome: may benefit from
Methylprednisolone pulses with cyclophosphamide (Mendoza protocol).
The recent guidelines advise against this protocol for SRNS.
Steroid pulse therapy :
- Methylprednisolone 10 mg/kg or 300 mg/m2 IV infusion every other
day for 3 doses followed by Prednisone 40 mg/m2 every other day.
- Kidney biopsy and genetic testing are essential to avoid excess
glucocorticoid toxicity
Steroid sparing medicines: Cyclosporine ,Tacrolimus, MMF
Anti proteinuric agents: ACE inhibitors and Angiotensin II Blockers(ARBs)
Supportive therapy
- Lipid-lowering drugs
- Thrombosis prophylaxis
- Vitamin D
Renal transplantation (Oxford Pediatric Nephrology)

Page | 248
N.B Drugs Complications

Steroids
Cataract
Ulcers (peptic) ĺadd ranitidine or proton pump inhibitor
Striae
Hypertension
Infections due to immunosuppression
Necrosis of bone ĺ may require calcium and vit D
Growth retardation ĺmonitor height Q 3 months
Osteoporosis
Intracranial hypertension
Diabetes Mellitus
Myopathy (proximal)
Adipose tissue hypertrophy (moon face, Bufflo hump, trunkal obesity)
Pancreatitis
Cyclophosphamide
Alopecia
Bone marrow suppression
Hemorrhagic Cystitis (prevented by I.V. Mesna)
Decreased fertility
Cyclosporin A
Hypertrichosis
Hypertension
Hyperplasia of gums
Nephrotoxicity
MMF
Leucopenia /anemia
GIT ulcerations
Tacrolimus
Hyperglycemia
Nephrotoxicity
Rituximab
Immunosuppression
Unclear long term safety profile
Causes of death in nephritic syndrome?
1. Renal failure
2. Overwhelming infections
3. Hypovolemic shock

Page | 249
Congenital and infantile nephrotic syndrome
¾ Congenital nephrotic syndrome (CNS):

Presentation of nephrotic syndrome during the first 3 months of life (often
present before or at birth)
¾ Infantile nephrotic syndrome :
Presentation of nephrotic syndrome between 3 and 12 months of age
Primary causes
Finnish-type CNS
Diffuse mesangial sclerosis
Focal segmental glomerulosclerosis
Membranous nephropathy
Minimal change disease
Secondary causes
Congenital Infections
Syndrome-associated:
- Denys Drash syndrome: Wilm’s tumor, genitourinary anomalies ,
nephrotic syndrome
- Nail-patella syndrome
- Lowe’s syndrome
- Frasier syndrome : Male pseudohermaphroditism and proteinuria
Other: e.g.
HUS
Nephroblastoma
Drug reaction

Page | 250
Fennish type congenital nephrotic syndrome

- Autosomal recessive disorder
- Most patients have mutations in the NPHS1 gene which encodes for Nephrin
protein in the glomerular basement membrane.
Presentation
Low birth weight
Large edematous placenta ( > 25 % mass of newborn)
Generalized edema
Histology: early tubular dilatation (microcytic change), later on glomerular
sclerosis and fibrosis ending in end stage renal failure
Treatment
Bilateral nephrectomies and peritoneal dialysis + Transplantation once the child
has reached approximately 9 –10kg
Alternatively, perform early unilateral nephrectomy plus medical therapy +
Second nephrectomy and subsequent transplantation at 3 – 4 years of age
Medical supportive therapy (as before)
Regular albumin infusions via a central venous catheter until bilateral
nephrectomy is performed
ACEI/ARBs.
NSAID e.g. Indomethacin up to 4mg/kg divided into three doses.
Thyroxine is necessary from birth.
Childhood vaccines should be completed after nephrectomy prior to
transplantation
Close attention to nutrition and growth — high calorie and high protein
diet (4mg/kg/day).
Anticoagulation with warfarin/aspirin may have a role.
(Oxford pediatric nephrology handbook)

Page | 251

Acute Renal Failure (ARF)
Definition: A sudden, potentially reversible inability of the kidney to maintain
normal body chemistry and fluid balance. The term ARF has been replaced by
the term Acute Kidney Injury (AKI).
Etiology
A. Pre renal (60%)
Due to: Marked reduction of renal blood flow
1. Excess losses
Gastro-enteritis
Polyuria &
Burns
Hemorrhage
2. Hypo albuminenic states

Nephrotic syndrome
Liver failure (hepato-renal synd.)
3. Impaired cardiac output

Heart failure
Shock
B. Intrinsic renal (30%)

Due to: Renal parenchymal damage
1. Glomerular: Acute glomerulonephritis
2. Tubular necrosis
- Untreated pre-renal failure
3. Interstitial
- Tubulointerstitial
- Nephrotoxins e.g.
nephritis
aminoglycosides
- Pyelonephritis
- Myoglobinuria
- Hemoglobinuria
- Crystal nephropathy
4. Vascular
- Renal vein thrombosis.
- Hemolytic uremic syndrome
5. Acute on top of chronic: Decompensated CKD due to inter current illness
C. Post renal (10%): Due to: urine outflow obstruction (Obstructive uropathy)
By stones, tumors, trauma

Page | 252
Clinical picture
1. Manifestations of the cause; basically in pre renal failure
2. Oliguric phase:
Mechanism Clinical sign
Water retention Oliguria or anuria
Edema
Hypertension
Waste retention Acidotic breathing (rapid & deep)
+\SHUNDOHPLDĺG\VUK\WKPLDV
8UHDĺXUHPLFHQFHSKDORSDWK\ FRQIXVLRQ
ĺFRQYXOVLRQVĺFRPD
Systemic upset Heart failure up to acute pulmonary edema
may occur due to hypervolemia
GIT bleeding may occur due to gastric stress
ulcers and thrombocytopathy
Convulsions may occur due to excessive salt
loss(hyponatremia) or uremic encephalopathy
3. Polyuric phase:
It PD\ RFFXU LQGLFDWLQJ HDUO\ UHFRYHU\ ĺ QHZ WXEXODU FHOOV FDQ¶W UHWDLQ
IOXLG HOHFWURO\WHVĺSRO\XULD HOHFWURO\WHORVV
Diagnosis
1. Is there an Acute Kidney Injury
Urine volume Oliguria:
Urine output < 0.5mL/kg/h
(< 300 ml/m2/day) or
< 1mL/kg/h in an infant
Anuria : urine output < 30 ml/m2/day
Renal function tests Elevated serum creatinine
Elevated urea & blood urea nitrogen(BUN)
Acid / base disturbance 0HWDEROLFDFLGRVLV ĻS+Ļ3D&22Ļ+&23).
Electrolytes Hyperkalemia.
Hyponatremia.
Hypocalcemia, hyperphosphatemia
Creatinine is an insensitive and delayed measure of decreased kidney

function. Other biomarkers under investigation include changes in plasma
neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C levels and
urinary changes in NGAL

Page | 253
2. For effect/cause
a) ECG: for evidence of hyperklemia
Tall peaked T wave; the earliest ECG sign of hyperkalemia
Widening of QRS complex
Arrhythmias
b) Ultrasonography
Exclude obstructive uropathy
Differentiate between acute (enlarged and echobright kidneys) and
acute on top of chronic failure (shrunken kidneys)
c) Radiologic studies:for
Heart failure: cardiomegaly with prominent pulmonary markings
Renal stones
3. Diagnosis of the type
i. Post renal
1- Palpable bladder & kidneys.
2- Bladder catheterization
3- Abdominal ultrasound to exclude obstructive uropathy.
ii. Pre renal iii. Intrinsic renal
Clinical Hypovolemia : Euvolemia or
Tachycardia Hypervolemia :
Core-peripheral Hypertension
temperature gap > 2 °C Raised jugular
Prolonged capillary refill venous pressure
time Tachycardia,
Dehydration
gallop rhythm
Hypotension
Palpable liver
Laboratory
Urine osmolality High Low
Urine specific gravity > 1020 < 1010
Urine sodium < 20 meq/L > 30 meq/L
Fractional excretion <1 >1
of Na(FNa)
BUN / creatinine > 20:1 10-20:1 (+ oliguria)
ratio(mg/dl)
US Normal Kidneys are enlarged
and echobright

Page | 254
Pediatric RIFLE (pRIFLE) criteria

Used for the detection and classification of AKI and for correlation with clinical outcomes
Serum creatinine rise GFR decline Urine out put
Risk 1.5-fold 25 % <0.5 ml/kg/h × 8 h
Injury 2-fold 50 % <0.5 ml/kg/h × 16 h
Failure 3-fold 75% or <0.3 ml/kg/h × 24 h or
< 35 ml/min/1.73 m2 anuric for 12 h
Loss Persistent failure > 4 weeks
End ESRD (persistent failure >3 months)
stage
Treatment of ARF
,+RVSLWDOL]DWLRQDQG0RQLWRULQJ
Weight ĺ Twice daily
Fluid input-output recording ĺ Hourly
Vitals; including BP ĺ Hourly
Blood sugar ĺ 6-hourly
Neurological observations ĺ Hourly
Renal parameters (BUN/Creatinine) ĺ May be appropriate to perform
Blood gases, Electrolytes up to every 6hours
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- )OXLGORVVĺVDOLQHinfusion 10 ml/kg over 30 minutes

- %ORRGORVVĺIUHVKEORRGWUDQVfusion
- 3ODVPDORVVĺSODVPDWUDQVIXVLRQ
- Protein loss (Nephrotic) ĺalbumin infusion
Repeat if necessary
:LWKJRRGFRUUHFWLRQĺthe patient should void within 1-2 hours

Page | 255

,97UHDWPHQWRILQWULQVLFUHQDOIDLOXUH
1. Monitoring
2. Maintain fluid balance:
Euvolemic Fluid challenge 10–20mL/kg normal saline over
1h with
Furosemide 2–4mg/kg IV
Hypervolemic Furosemide 2–4mg/kg IV
Maximum dose of diuretic = 12mg/kg/day
Value : Reduce volume overload & enhance potassium excretion
If there is no response to a diuretic challenge, diuretics should be
discontinued and start fluid restriction / Dialysis
Fluids intake
Daily intake = insensible loss (400 ml/m2 or 30mL/kg/day) + plus
urine output and other ongoing losses
Type: feeds if tolerated or IV D5 / Half normal saline
Replace 100 % of urine output if euvolemic.
Restrict to 50–75 % of urine output if overloaded
Nutrition
Consult renal dietician
Maximize caloric intake
Restrict sodium, potassium and phosphorus and proteins
3. Management of electrolyte and acid base abnormalities
a. Hyperkalemia SRWDVVLXPOHYHOPHT/
Restrict potassium intake
Enhance GIT excretion by kayexalate (polyestrene resin) oral or enema.
With potassium levels above 7 meq/l or ECG changes appear
R Stabilize cardiac membrane by 1 ml/kg calcium gluconate 10%
slow I.V
R Shift potassium intracellular by:
Salbutamol nebulizer
Sodium bicarbonate 1-2 mEq/kg over 10 minutes i.v
Regular insulin(0.1 u/kg) + glucose 50% solution(1 ml /kg)
over 1 hour
Persistent hyperkalemia should be managed by dialysis
b. Hyponatremia (sodium level < 130 meq/L):
Dilutional hyponatremia usually respond to fluid restriction
Hyponatremia < 120 meq/l with seizures is treated with Na CL 3%
(Target serum sodium 125 mEq/l)

Page | 256
c. Hypocalcemia and hyperphosphatemia

Tetany is rare as acidosis increases ionized calcium.
Restrict phosphate intake & give phosphate binders e.g. sevelamer
(Renagel), calcium carbonate or calcium acetate (PhosLo).
Calcium gluconate 10 % slow iv only for cases with tetany
d. Metabolic acidosis
Slow partial correction with IV bicarbonate 1–2mmol/kg
Monitor serum calcium
4. Treatment of complications
$QHPLDĺ)UHVKSDFNHG5%&VWUDQVIXVLRQRYHU- 6 hours
+\SHUWHQVLRQĺ'LXUHWLFV,VUDGLSLQHDPHORGLSLQHHWF
5. Dialysis
Indications
Clinical
1. Volume overload with evidence of hypertension and/or pulmonary
edema refractory to diuretic therapy
2. Neurologic symptoms (altered mental status, seizures)
3. Inability to provide adequate nutritional intake because of the need for
severe fluid restriction(dialysis provides a space for nutrition)
Laboratory
1. Persistent hyperkalemia
2. Severe metabolic acidosis unresponsive to medical management
3. Blood urea nitrogen >100-150 mg/dL (or lower if rapidly rising)
4. Calcium: phosphorus imbalance, with hypocalcemic tetany
Modes of dialysis
1) Peritoneal dialysis : most commonly employed in neonates and infants
with ARF
2) Continual Renal Replacement Therapy (CRRT): useful in patients with
unstable hemodynamic status, concomitant sepsis, or multiorgan
failure in the intensive care setting
3) Intermittent hemodialysis: useful in patients with relatively stable
hemodynamic status
Prognosis
The mortality rate depends entirely on the nature of the underlying disease
Recovery of renal function is likely after ARF resulting from prerenal
causes, HUS, Acute tubular necrosis, or acute interstitial nephritis.
Poor outcome with AKI following rapidly progressive glomerulonephritis,
bilateral renal vein thrombosis, or bilateral cortical necrosis

Page | 257
Chronic kidney disease (CKD)

Chronic Renal Failure (CRF)
Definition
Irrecoverable, bilateral abnormalities of the renal parenchyma ĺ
permanent reduction of glomerular filtration rate (GFR)
CKD has reSODFHG³FKURQLFUHQDOIDLOXUH´DQG³FKURQLFUHQDO
LQVXIILFLHQF\´DVWKHJOREDOO\DFFHSWHGWHUPLQRORJ\IRUSHUVLVWHQWUHQDO
dysfunction
Stages of CKD
CKD stage Description GFR (ml/min/1.73 m2 )
1 Kidney damage with
normal or increased GFR
2 Kidney damage with 60–89
mild decrease in GFR
3 Moderate decrease in 30–59
GFR
4 Severe decrease in GFR 15–29
5 Kidney failure <15 (or dialysis)
(Manual of pediatric nephrology)
Causes
In < 5 years of age
Congenital malformations:
Hypoplastic/dysplastic kidneys
Reflux nephropathy(VUR+UTI)
Obstructive uropathy
Metabolic/genetic disorders:
Oxalosis
Polycystic kidney disease
Congenital nephrotic syndrome
:LOPV¶WXPRU
In > 5 years of age
Glomerular disease:
Focal segmental glomerulosclerosis
Hemolytic uremic syndrome
Chronic glomerulonephritis
$OSRUW¶VV\QGURPH
Tubulointerstitial disease:
Chronic tubulointerstitial nephritis
Cystinosis
Nephrotoxic drugs

Page | 258
Clinical picture
Non specific so, need high index of suspicion
Clinical feature Mechanism
R Growth retardation (Short stature) - Resistance to growth hormone
- Anemia
- Anorexia ( metabolic acidosis)
- Renal osteodystrophy
R Unexplained anemia - p Erythropiotine
- Ļ intake of iron, B12, folic acid.
- Bone marrow depression by uremic toxins
- Defective iron utilization.
R Polyuria / Polydipsia/ Nocturia - Renal tubular concentration defect
R Hypertension - Increased renin & fluid retention
R Renal osteodystrophy (ROD) - Hyperphosphatemia
- Decreased 1,25 (OH)2D3
- Secondary hyperparathyriodism
R Bleeding tendency - Platelet dysfunction
R Infection - Defective granulocyte function
R Neurologic (fatigue , - Uremic toxins
drowsiness,polyneuropathy)
R Pericarditis, cardiomyopathy - Uremic toxins - Hypertension
R Hyperlipidemia - ĻOLSRSURWHLQOLSDVHDFWLYLW\
R Hyperkalemia and hyponatremia
Diagnosis
1. Assessment of renal function:
Serial measurements of creatinine: An abnormal serum creatinine value
persisting for more than 3 months confirms CKD.
Estimated GFR by 6FKZDUW]¶VHTXDWLRQ & DTPA scan
Proteinuria: Persistent proteinuria is a marker of ongoing renal disease.
2. Renal ultrasound & DMSA scan show shrunken kidneys(Kidneys may appear
large e.g. Polycystic kidney disease , Obstructive uropathy)
3. For complications:
CBC for anemia
Lipid profile
Echocardiography for pericardial effusion & cardiomyopathy.
In ROD ĺ High phosphate - low calcium - high intact PTH
ĺBone X-UD\ĺVXESHULRVWHDOHURVLRQVERQHF\VWV
4. For the cause
5. Follow up investigations (see later)

Page | 259
Treatment
Stages of treatment:
Stage 1: diagnosis and treatment of primary disease
Stage 2- 3: retard progression, treat complications/comorbidities
Stage 4: prepare for renal replacement therapy
Stage 5: renal replacement
Outpatient checks in the child with CKD

Height, weight and head circumference
Pubertal stage
BP
Investigations at each clinic visit

1. Full blood count (FBC; and ferritin if needing an erythropoiesis
stimulating agent).
2. Urea & electrolytes (U&Es), bicarbonate, and creatinine
3. Calcium, phosphate, albumin, alkaline phosphatase, intact PTH
4. Urine protein or albumin to creatinine ratio
5. Fasting HDL and LDL, total cholesterol and triglycerides 6 monthly.
Management
A. Slowing the progression of chronic kidney disease
1. Control proteinuria
Rate of decline of kidney function is closely related to the quantity of
proteinuria
Use:
9 Angiotensin Converting Enzyme Inhibitors; enalapril or captopril
and/or
9 Angiotensin Receptor Blockers(Irbesartan)
2. Control hypertension
BP should be maintained within the normal range for age and height
There is some evidence that BP <50th centile may be beneficial
3. Control Dyslipidaemia by
Dietary intervention
Statins
4. Treatment of anemia

Page | 260
B. Conservative treatment
Nutrition
Consult expert dietician
Treat vomiting (ranitidine)
High caloric diet
Dietary supplements, either orally or enterally, via nasogastric tube or
gastrostomy, if anorexic
Protein and potassium restriction may be needed in stage 4-5 CKD!
Feeding infants with CKD:
Breast milk
Special formula e.g. Low salt formula (SMA), high energy formula
(Maxijul), low potassium , low phosphate formula (Renastart),….
Fluid and electrolyte balance
,ISRO\XULDĺIUHHDFFHVVWRZDWHU
,IVDOWDQGELFDUERQDWHORVHUĺVDOWDQGELFDUERQDWHsupplementation
Growth
Correct acidosis, hyperparathyroidism and anemia
Optimize nutrition
Recombinant human growth hormone (rhGH)
Anemia
Target Hb should be in the range of 11.0–12.0 g/dl
Iron supplement
Erythropoietin 50-100 U/kg/week or Darbepoetin D (longer half-life)
RBCs Transfusion for symptomatic severe anemia
Mineral and bone disorder (ROD)
The target range of serum PTH is closely related to stage of CKD
Treatment
1. Control hyperphosphatemia
x Dietary phosphorus restriction
x Phosphate binders;administered with meals
Calcium based e.g. Calcium carbonate, calcium acetate
Non calcium based: Sevelamer (Renagel)is now more popular
2. Maintain serum calcium
3. Vitamin D therapy: One Alpha = 1 D (OH) D3 and Calcitriol
4. Ca sensing receptor blockers, Cinacalcet, blocks calcium sensing
receptors (CaSR) in parathyroids ĺReduce PTH.
5. Partial parathyroidectomy for treatment - resistant tertiary
hyperparathyroidism with persistent hypercalcemia

Page | 261
Hypertension (HTN)
Target blood pressure should be lower than the 90th percentile for
normal values adjusted for age, gender, and height
Maintaining BP below the 50th percentile may be effective in
delaying progression of CKD
Use
Diuretics
ACEI/ARBs
Calcium channel blockers
Beta blockers
Immunizations
All children must complete all routine childhood vaccines.
BCG, Varicella, pneumococcal polysaccharide (PPV) and hepatitis B
vaccines must be added in children approaching RRT
Annual influenza vaccine
Transplantation can be delayed till vaccination schedule is completed
C. Renal replacement therapy (RRT)
Dialysis
Indications:
Laboratory criteria: GFR <15 ml/min/m2
Refractory hyperkalemia, hyperphosphatemia,
and metabolic acidosis
Clinical criteria Children with symptoms of
Nausea, vomiting
Malnutrition, growth retardation
Fluid overload, hypertension
Uremia
Despite optimal medical management
Types
Hemodialysis
Chronic peritoneal dialysis
Renal transplantation
The renal replacement therapy of choice in children
Offering a near normal life to a child with end-stage renal disease

Page | 262
Urinary Tract Infections

Urinary tract infections can present as
x Upper urinary tract infections o acute & chronic pyelonephritis
x Lower urinary tract infections o acute & chronic cystitis & urethritis
x Asymptomatic bacteruria
x Septicemia
Causes
Risk factors Common organisms
Females (short urethra) - G -ve o - Escherichia coli (80%)
Uncircumcised boys - Proteus (more in boys)
Vesico ureteric reflux(VUR) - Pseudomonas
Obstructive uropathy - G +ve o staph, strept. fecalis
Constipation
Instrumentation
Causes of recurrent UTI
1. Obstructive uropathy:
- VUR either congenital or secondary to UTI
- Congenital anomalies e.g. phimosis
- Renal calculi
- Neurogenic bladder
2. Catheters or foreign bodies
3. Constipation; elimination disorders
4. Mal treatment or inadequate treatment of an acute attack
Clinical picture: (presentation differs according to age)
Asymptomatic bacteruria: - positive urine culture without manifestations
Newborn Sepsis (Jaundice,p feeding,………)
Infant Fever ( UTI is the most common bacterial
cause of fever without focus in infants)
Screaming during micturition
Failure to thrive(vomitingo weight loss)
Child Lower UTI - Urgency, dysuria, frequency
- Suprapubic pain
- 2ry nocturnal enuresis
- May be hematuria
Upper UTI - $FXWHĺ)HYHUULJRUV ORLQSDLQ
- &KURQLFĺ3URORnged fever
ĺ0D\EHK\SHUWHQVLRQ

Page | 263

Investigations
1. Diagnosis of urinary tract infections: by Urinalysis and culture
Urine sample obtained by:
For toilet-trained children
Mid-stream voided urine
For non-toilet-trained children
Clean catch into a waiting sterile pot when the nappy is removed
Urine bag (high a rate of contaminationĺunreliable culture results)
If UTI is suggested; order a urine culture using a sample by either
In and out catheter sample; reliable and more practical than SPA
Suparpubic aspiration; SPA (Reserved for sick patients)
Findings
Pyuria:
5WBCs/hpf 2U 10 WBCs/ml
[Absence of pyuria is rare if UTI is present]
Leukocyte esterase and Nitrite tests are usually positive with UTI
Gram stained films: For bacteruria
Urine culture: necessary for confirmation and appropriate therapy
Minimum colony counts indicative of a urinary tract infection:
Specimen (CFU/mL)
Clean catch (midstream) 5
Catheter î4
Suprapubic aspiration Any growth
2. Indicators of upper UTI (Acute pyelonephritis):
Leukocytosis, neutrophilia
Elevated serum erythrocyte sedimentation rate and C-reactive protein
Blood cultures, particularly in infants and in obstructive uropathy
DMSA scan
3. Imaging studies:
Imaging tools Yield

Ultrasound of kidneys Assess kidney size , anatomy and position
and bladder Evaluate bladder wall thickness and
emptying
Detect ureteral dilation
Detect hydronephrosis

Page | 264

MCUG (Micturating Cyst The gold standard investigation for the
Urethro Gram) diagnosis of urethral abnormalities and
VUR
Evaluate bladder anatomy and emptying
Plain abdomen Fecal masses
Spinal dysraphism
DMSA scan The gold standard investigation for the
diagnosis of renal parenchymal damage
Acute : diagnose acute pyelonephritis
Chronic : detect renal scarring
NICE Guideline for imaging in UTI
Ultrasound
Indicated during the acute infection for:
Infants below 6 months
Atypical UTI
Recurrent UTI
MCUG
Done at 2-4 weeks post UTI allowing bladder inflammation to
resolve
Indications:
1. After a second UTI is diagnosed
2. After a first UTI with:
Abnormal ultrasound findings e.g. hydrnephrosis, scarring,
obstructive uropathy or VUR
Poor urine flow
Non E.coli UTI
Family history of vesico ureteral reflux VUR
DMSA scan
Done at 4-6 months in order to avoid a false positive result due to
renal parenchymal inflammation that may resolve
Indications:
Child > 3 years of age with clinical pyelonephritis
Atypical UTI
Recurrent UTI
In children with infection of the lower urinary tract, imaging is
usually unnecessary.
Instead, assessment and treatment of bladder and bowel
dysfunction is important.
If there are numerous lower urinary tract infections, then a renal
sonogram is appropriate

Page | 265

Treatment
NICE guidelines regarding antibiotic treatment
Age Antibiotic Plan
Age < 3 months IV antibiotics for 2–4 days then
Switch to oral antibiotics if clinically improved
Age > 3 months with upper Oral antibiotic for 7–10 days
tract UTI IV antibiotics for 2–4 days if vomiting, then
oral antibiotics for a total of 10 days
Age > 3 months with lower Oral antibiotics for 3 days
urinary tract symptoms
If a child is on prophylaxis Change the antibiotic
(Oxford pediatric nephrology)
Empirical antibiotics
Oral antibiotics e.g. Parenteral antibiotics e.g.
Cotrimoxazole Ceftriaxone
Amoxicillin Cefotaxime
Cefixime Ampicillin plus an
Ciprofloxacin for resistant cases aminoglycoside e.g. gentamicin
Follow on
x Change antibiotics according to culture and sensitivity
x Urine culture after 1 week to ensure recovery
x Continue antibiotics till urine culture turns sterile, pyuria disappears,
afebrile without clinical evidence of UTI
x Urine culture after 3 months o detect recurrence
Supportive care
Adequate hydration
Diet, rest and symptomatic treatment e.g. antipyretics
Admit to hospital sick children (dehydrated, vomiting, PRRIDJH)
Prevention: For recurrent urinary tract infections
Treat risk factor e.g. stones, constipation, voiding dysfunction
Adequate hydration
Frequent bladder emptying
Antibiotic prophylaxis
e.g. Low dose cotrimoxazole or nitrofurantion
For high risk conditions e.g. neurogenic bladder, and VUR
Usually for patients below 3 years
Probiotic and cranberry juice may have added benefit

Page | 266
Enuresis
Definitions
x Most children achieve night-time dryness by 5 years of age, when
x bladder volume exceeds nocturnal urine production
x Nocturnal enuresis is involuntary loss of urine at night, in the absence of
physical disease, at an age when the child could reasonably be expected to
be dry (developmental age of 5 years by consensus)
x Nocturnal enuresis is common, affecting 15–20 % of 5-year-olds, 5 % of
x 10-year-olds and 1–2 % of 15-year-olds
x Enuresis differs from urinary incontinence that in enuresis the child can
control bladder while incontinence means loss of bladder control
Clinical types:
Primary: the child has never been dry
Secondary: the child has previously been dry at night for 6 months or more
after the age of 5 years;
Monosymptomatic (uncomplicated): not associated with other urinary tracts
symptoms
Polysymptomatic (complicated) :associated with symptoms suggestive of
lower urinary tract dysfunction
Etiology:
Poorly understood
Developmental disorder: Delay in maturation of bladder control
Strong genetic component: a family history is found in most children
Psychological disturbances e.g. emotional deprivation
Organic causes e.g. mental retardation, urinary tract infections, polyuria as
in diabetes mellitus or insipidus.
Management:
1. Proper history taking.
2. Investigations to exclude organic causes.
3. Psychotherapy if emotional factors are present.
General measures
Adequate daytime fluid intake to develop bladder capacity and reduce
evening fluid intake
Avoid caffeine-based drinks
Exclude/treat constipation if present
Consider correction of airway obstruction in heavy snorers
Pass urine regularly during the daytime and before sleep
Waking for toileting is used only as short-term management

Page | 267
Reward systems
Star charts for dry nights
Rewards should be given for agreed behavior e.g toileting before sleep,….
Where these measures alone are unsuccessful, consider the use of an
alarm system or drug treatment
Alarm systems
With alarm system around 50 % of children
achieving long-term dryness
Alarm systems are superior to behavioral
techniques and drug therapy
Use until either 14 consecutive dry nights or 3
months
Alarms and desmopressin equally effective but
alarm has more prolonged effect
Drawbacks: requires time, motivation, and hard work
Desmopressin
Has more immediate effect than alarm
May be used “on important nights only”
Where successful, treatment should be withdrawn
every 3 months to assess response
Dosage: oral tablets 0.2–0.4 mg or 120–240
micrograms sublingually at bed time
Keep evening fluid intake below 200 ml and no
nighttime drinking
Stop treatment if no effect within 2 weeks
Drawbacks: high relapse rate upon stopping
Can be combined with alarm
Anticholinergics e.g. Oxybutynin

May be considered for cases unresponsive to the above therapy
With or without desmopressin/alarm
Never combined with tricyclic antidepressants
Exclude residual urine and/or constipation
Useful for cases with day time wetting
Tricyclic antidepressants (Imipramine)
Restricted to those who have not responded to alarm and/or desmopressin
Have significant adverse-effects ; cardio toxic ,anticholinergic effects
If used, imipramine should be withdrawn gradually

‫‬
‫\‪*DVWURHQWHURORJ‬‬
Page | 268
Causes of vomiting in infants and children

1. Acute infections 2. Metabolic 3. Acute intestinal obstruction
- CNS infections - Drug poisoning * Functional: Paralytic ileus
- Pulmonary infections - Rye’s syndrome * Organic:
- Gastroenteritis - Diabetic keto acidosis - Intussusception
- Acute pyelonephritis - Renal failure - Volvulous
- Sepsis - Drugs: e.g. aspirin
4. Chronic vomiting
- Over feeding
- Gastro-Esophageal reflux
- Congenital pyloric stenosis
- Inborn errors of metabolism/ adrenal insufficiency
- Psychogenic
Causes of Abdominal pain
i- Acute abdominal pain
Acute infections Acute medical conditions Acute intestinal
- Strept. Pharyngitis - Pneumonia(lower lobe) obstruction
(mesenteric adenitis) - Rheumatic fever (peritonitis)
- Acute hepatitis. - Henoch Schonlein purpura.
- Acute pancreatitis - Familial mediterranean fever.
- Acute pyelonephritis - Diabetic keto acidosis
- Acute appendicitis.
- Acute peritonitis.
ii- Chronic (recurrent) abdominal pain
Functional Organic
- Irritable bowel syndrome - Intestinal parasites e.g. Giardiasis
(in 90%; psychic related) - Chronic diarrhea (and Malabo sorption)
- School phobia - Chronic constipation
- Inflammatory bowel disease
- H. Pylori infection
- Chronic hepatitis
- Stones (urinary, biliary)
Q. Causes of constipation?
- Anal fissure
- Spina bifida
- Cretinism
- Intestinal obstruction
- Habitual constipation
- Medications (narcotics)

Page | 269
Stomatitis
Definition: Inflammation of the oral mucosa
Clinical types
1. Catarrhal stomatitis:
Mild generalized inflammation of the oral mucosa
Causes
It accompanies acute infections as measles
Local factors (chemical, traumatic or thermal).
Treatment: may use gentian violet 1 % or local oral anesthetics
2. Herpetic gingivo-stomatitis:
Caused by herpes simplex virus
Clinical picture
a. Acute onset of fever, anorexia; few days later
b. Herpetic vesicles appear o minute ulcers
c. Associations:
Pain, excessive salivation
Bad mouth odor
May be bleeding, swollen gums.
Treatment (Nelson 2016)
Care of feeding: cold fluids ± nasogastric tube feeding in severe cases.
Mouth paint with gentian violet 2% or silver nitrate 2%.
Antiviral agents as Acyclovir (Zovirax).
3. Thrush stomatitis (Moniliais):
Caused by candida albicans in:
New born: infected from mothers with genital moniliasis or infected teats
Malnourished infants due decreased cell mediated immunity
As a side effect of excess use of antibiotics.
Clinical picture
Numerous small white flakes
On the dorsum of tongue, inner side of
cheeks & palate.
In extensive cases a thick white
membrane is formed
Prevention
The nipple and areola of the nursing mother should be cleaned before feeding
and painted with nystatin ointment in between meals.
Treatment

Page | 270
4. Gangrenous stomatitis:
Rare; Seen in severe debilitated children with diseases as measles
A deep large ulcer on the inn surface of the cheeks that spread slowly by
necrosis of adjacent tissues
It may lead to perforation of the cheek
Treatment: antibiotics plus surgical excision of necrotic areas.
Differential diagnosis of oral ulcers

Common Criteria
Aphthous (canker sore) Painful
Circumscribed lesions
Last 10-14 days
Recurrences
Treatment: benzocaine and topical lidocaine,
are effective, as are topical steroids
Traumatic Accidents
Chronic cheek biter
Hand, foot, mouth disease Painful
Lesions on tongue, anterior oral cavity, hands,
and feet
Herpangina Painful
Lesions confined to soft palate and
oropharynx
Herpetic gingivostomatitis Vesicles on mucocutaneous borders
Painful
Febrile
Uncommon
R Neutrophil defects Agranulocytosis, leukemia, cyclic neutropenia
Painful
R Systemic lupus Recurrent
erythematosus May be painless
R Behçet syndrome Resembles aphthous lesions
Associated with genital ulcers, uveitis
R Oral Crohn’s disease Aphthous-like
Painful
R Stevens-Johnson syndrome May be isolated or appear initially in the oral
cavity

Page | 271
Achalasia
Definition
Esophageal motility disorder characterized by:
Failure of relaxation of lower esophageal sphincter (LES)
Due to lack of ganglionic cells in the lower esophageal sphincter
With subsequent increased lower esophageal sphincter pressure
Incidence: most cases occur after age of 15 years
Clinical picture
Dysphagia mainly to liquids rather than to solids that may open LES by
weight
Regurgitation of food
Cough due to overflow of fluids into trachea (frequent aspiration)
Recurrent chest infections
Failure to gain weight in progressive cases
Diagnosis
Upright chest x ray show air fluid level in dilated esophagus
Barium swallow fluoroscopy shows massive dilatation of the esophagus
with tapered lower end
Esophageal manometry is diagnostic; it reveals:

9 Aperistalsis in the distal esophageal body and
9 Incomplete or absent LES relaxation, often accompanied by
9 High pressure LES
Treatment
Pneumatic dilation is the initial treatment of choice, and does not preclude
a future myotomy
Temporary relief of dysphagia can be offered by calcium channel blockers
(nifedipine) and phosphodiesterase inhibitors or endoscopic intra
sphincteric injection of botulism toxin
Heller myotomy: surgical division of muscles at gastroesophgeal junction.

Page | 272
Gastro- Esophageal Reflux Disease (GERD)
Definition: Abnormal retrograde of gastric contents into oesphagus due to

persistent relaxation of lower oesphageal sphincter (LES)
Incidence: - Mainly in neonates & young infants
- 60% improve with age (resolve by 6 mo-2years).
Clinical picture
A. Uncomplicated cases
1. Vomiting
At the end of the feed
From the 1st week of life
Increase with lying flat
May be bile stained.
2. Sandifer syndrome: abnormal head posture and opisthotonus to protect
airways.
3. Substernal pain and dysphagia in older child
B. Complicated cases
Oesphagitis o GIT bleeding
Recurrent aspirations o recurrent aspiration pneumonia
Chronic cough & chest wheezes
Growth retardation
May be sudden infant death syndrome(SIDS) due to laryngospasm and
apnea
Investigations
1. Diagnostic:
Radiologic
Barium swallow under screen o retrograde of the dye
Doesn’t assesses mucosal inflammation nor the severity of GERD
Extended esophageal pH monitoring: PH< 4 in 5-8% of the monitoring
time
Endoscopy
Detects low LES pressure by manometry
Detect acidic esophageal pH (< 4)
Visualize erosive esophagitis and
complications such as strictures or
Barrett’s esophagus
2. For complications:
Check stool for occult blood Normal esophagus versus Erosive esophagitis

Page | 273
Treatment
Medical
Feeding : Thickening feedings with rice or oat cereal (1tablespoon/ounce)
Position
Head up for 30 min after feeding. However, the “infant seat” may
worsen reflux by increasing intraabdominal pressure
Supine position reduces SIDS but worsen GERD
When the infant is awake and observed, prone position and upright
carried position can be used to minimize reflux.
Pharmacotherapy
R Ameliorate acidity by:
Anti-acids
Histamin-2 (H2) receptor blockers e.g. Ranitidine
Proton pump inhibitors(PPIs) e.g. omeprazole, esomeprazole
R Prokinetics: controversial and not recommended
Domperidone (Risk of cardiac dysrhythmias)
Metoclopramide (Risk of tardive dyskinesia)
Baclofen ; DFHQWUDOO\DFWLQJȖ-aminobutyric acid agonist
Under research: Metabotropic glutamate receptor 5 antagonists
Avoid methylexanthines o it lowers LES tone
Surgical
Operation
Fundo plication
Indications
Failed medical treatment
Complications. e.g. Growth retardation

Page | 274
Congenital Hypertrophic Pyloric Stenosis

Definition
Progressive hypertrophy of circular muscles fibers of the pylorus with
subsequent pyloric narrowing due to ganglionic cells immaturity
Pathogenesis
Progressive vomiting results in:
- Loss of HCLo metabolic alkalosis
- Loss of potassium and chloride o hypokalemia and hypochloremia
- Loss of water and nutrientso dehydration and failure to thrive
Clinical picture
Incidence
Males (especially first born) affected than females.
Positive family history may exist.
Symptoms
1. Vomiting:
Occurs shortly after feeding.
Usually starts after the 2nd – 3th weeks of life (Rarely before or after)
Initially, non-projectile then projectile
Non bile stained.
Baby is often hungry after vomiting.
2. Constipation; passage of small, infrequent stools
Examination
Baby is marasmic & dehydrated
Palpable mass (olive

tumor):
Visible peristalsis
In the right
from the left to the
hypochondrium
right
Mobile & non tender

Page | 275
1. Gastroesophageal reflux disease
2. Adrenal insufficiency (metabolic acidosis and elevated serum potassium
and urinary sodium concentration)
3. Inborn errors of metabolism can produce recurrent emesis with alkalosis
(urea cycle) or acidosis (organic acidemia) and lethargy, coma, or
seizures.
4. Gastro enteritis
5. Other anomalies: pyloric membrane or pyloric duplication, Duodenal
stenosis
Investigations
1. For diagnosis
A. Barium meal demonstrates:
Elongated narrow pyloric

Canal “string sign”
Parallel streaks of barium Markedly dilated
seen in the narrowed stomach
channel “double tract
sign”
Bulge of pyloric muscle into

antrum “shoulder sign”
B. Abdominal ultrasound: Confirms diagnosis with 95% sensitivity

Criteria for diagnosis:
2. For complications
* Hypochloremic metabolic alkalosis (npH, pCL)
* Hyponatremia & hypokalemia

Page | 276
Treatment
1. Surgical: 5DPVWHGW¶VS\ORURP\RWRP\
Pre-operative o correct electrolytes disturbance and dehydration
Post-operative o start small feeds o gradually increasing
Efficiency :100% curative
2. Medical: Not efficient, it includes:

Antispasmodic before feeds
Small, thick, frequent feeds
Keep upright for 1 hour after feeding

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Congenital Aganglionic Megacolon
(Hirsch sprung Disease)

Definition
Functional obstruction of the colon due to absence of ganglion cells in bowel wall
Commonest site: rectosegmoid in 75%
Incidence
1 / 5000
Male: Females = 4: 1 (positive family history may be present).
Clinical picture
1. Presentation may be:
Neonatal (80%): Delayed passage of meconium beyond 48 hours.
May be acute obstruction
In older child: Chronic constipation and abdominal distension.
Large fecal mass felt in left lower abdomen with
empty rectum
2. Complicated cases:
Enterocolitis:
Infection with clostridia difficile, staph aureus and anaerobes
Presented with bloody diarrhea & toxemia
Intermittent attacks of intestinal obstruction.
Failure to thrive due to protein losing enteropathy
Investigations
1. Rectal suction biopsy (from narrow segment)
The gold standard for diagnosing Hirschsprung disease
Reveals absent ganglia
2. Barium enema:
Unprepared contrast enema aid in the diagnosis in
children older than 1 month of age
Classic findings: an abrupt narrow transition zone
between the normal dilated proximal colon and a
smaller caliber obstructed distal aganglionic segment
Treatment
1. Surgical repair.
2. Preparation before surgery:
- Regular evacuation of rectum.
- Antibiotics.

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Hepatology
Functions of the liver
Synthesis of all proteins (except gamma globulin and F VIII)
Synthesis and excretion of Bile.
Synthesis and excretion of cholestrol.
Carbohydrate: - Post prandial o convert glucose to glycogen.
- Fasting o convert glycogen to glucose.
Detoxication e.g. converts ammonia to urea.
N.B Hepatic enzymes
:
n Intra cellular; (Markedly raised in hepatitis):

- Alanine aminotransferase (ALT); more specific to the liver.
- Aspartate aminotransferase (AST).
o Intra canalicular o Alkaline phosphatase, Gamma glutamyle transferase,
5 Nucleotidase markedly raised in cholestaisis.
Causes Hepatitis
Metabolic Toxic
With some inborn errors of x Drug e.g.: - INH, rifampicin
metabolism e.g. - Paracetamol overdose
1- Glactosemia
2- Wilson disease x Toxins e.g.: Mush-Room.
3- D1 antitrypsin deficiency.
4- Tyrosinemia.
Infections
Bacterial Protozoa Parasitic
- Septicaemia - Malaria - Bilharsiasis

- Enteric fever - Toxoplasma - Hydatid cyst.
- Brucellosis
Viral
Hepatotropic Non hepatotropic

Viruses attack the Viruses may cause hepatitis
liver mainly during its course
e.g.
Enterally transmitted Parenterally transmitted - EBV
- CMV
- Hepatitis A virus (HAV) - Hepatitis B virus (HBV) - Herpes viruses
- Hepatitis E virus (HEV) - Hepatitis C virus (HCV) - Rubella
- Hepatitis D virus (HDV)

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Acute Viral Hepatitis

Enteral viruses
Include hepatitis A (HAV) and Hepatitis E viruses (HEV)
Criteria
Excreted only in stool (not in body fluids) so infection occur by faeco-oral
route via contaminated water & food.
None enveloped RNA viruses.
Incubation period is short (2-6 weeks).
Epidemiology:-
Occur in epidemics (highly contagious) or sporadic.
Mainly in low socioeconomics
HAV is the commonest cause of acute viral hepatitis in school age.
HEV is rare in children.
Outcome
Complete recovery is the rule; no carrier state nor chronic hepatitis.
Fulminant hepatic failure may rarely occur.
HEV has high fatality in pregnant women.
Hepatitis A Virus (HAV)

(Infective Hepatitis)
HAV is the commonest cause of acute viral hepatitis in school age.

Pathology of acute hepatitis
Hepatocyte injury is due to cytopathic effects
Cholestatic jaundice with elevated both direct and indirect bilirubin
Clinical picture of acute hepatitis
R Many cases of viral hepatitis pass asymptomatic.
R Symptomatic cases pass in following phases:
I. Pre-icteric phase (2 – 4 weeks)
Fever, malaise
Anorexia, nausea, vomiting
Abdominal pain
Diarrhea is frequent in children while constipation predominates in adults
II. Icteric phase (2-4 weeks)
Improved previous symptoms with appearance of:
Jaundice
Tender hepatomegaly
Dark urine + pale stool

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III.Convalescent phase
Most patients achieve full recovery
2 distinct complications can occur
Complications
1. Acute liver failure (ALF)
Incidence: Very rare
Risk factors: adolescents and adults, immunocompromised patients and
those with underlying liver disorders
In the USA, HAV represents < 0.5% of pediatric-age ALF
In endemic areas of the world, HAV represents up to 40% of all cases
of pediatric ALF
Clinically:
Deep progressive jaundice
Bleeding tendency (p coagulation factors)
Generalized edema with ascites
Disturbed sleep rhythm, tremors, stupor & coma
Fate:
High mortality rate
Definitive treatment is liver transplantation.
2. Prolonged cholestatic syndrome
With problematic pruritus and fat malabsorption
Waxes and wanes over several months
Investigations
A. To prove acute hepatitis:
1. Liver function tests:
Aminotransferase levels (ALT & AST)
Markedly elevated; in thousands
The elevation level does not correlate with the extent of
hepatocellular necrosis nor to the prognosis
Serum bilirubin
Moderately elevated ;mainly conjugated
The first marker to normalize with recovery
Alkaline phosphatase o mildn
Albumin and prothrombin time o usually normal
2. Urine: Dark color due to n cholebilirubin and bile salts
3. Stool: Pale color due to p stercobilinogen.

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In ALF:
1. Aminotransferases rise initially then rapidly decline with rising bilirubin
2. Altered synthetic function:
9 The most important marker of liver injury and defining severity
Abnormal protein synthesis (prolonged prothrombin time, low serum
albumin levels)
Metabolic disturbances (hypoglycemia, lactic acidosis,
hyperammonemia)
B. For the cause o viral serology; HAV markers
Marker Significance
Anti – HAV (IgM) Recent HAV infection.
Anti – HAV (IgG) Previous HAV infection or HAV vaccination;
confers long-term protection
Management
General
Exclusion of school or child care till one week after clinical jaundice
Hand washing after defecation or dealing with infected child
Sterilization of toilet after use
HAV prophylaxis
Indications:

x

x

HAV vaccine (e.g. Havrix):
Inactivated vaccine, approved
Dose: 2 doses 6 months apart, IM.
Treatment


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‫‪3‬‬ ‫‪Illustrated Baby Nelson‬‬
‫‪Hepatitis E virus‬‬
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Page | 284
Parenteral viruses
Include Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Hepatitis D virus
(HDV)
Criteria:
Acute hepatitis due to parenteral viruses occur sporadically not in epidemics
HBV HCV HDV (Delta virus)
Nature Enveloped DNA virus. Non Non enveloped RNA virus
enveloped o need HBV coat to be
RNA virus. infective (defective virus;
dependent on HBs Ag).
Risk factors Perinatal exposure to an infected mother (The most important
risk factor for acquisition of HBV in children )
Parenteral via:
Post transfusion ; via contaminated blood products (The
most important risk factor for acquisition of HCV)
Hemodialysis patients
Drug abusers
Sexual
No risk factors identified in approximately 40% of cases
Incubation
2-6 months 2-4 months
period
Pathology of acute hepatitis
Hepatocyte injury can be due to:
Cytopathic effects (by all except HBV)
Immune mediated cell lysis (by HBV & HCV)
Cholestatic jaundice with elevated both direct and indirect bilirubin
In perinatal HBV infection : markers of infection and antigenemia appear
1-3 mo after birth
Clinical picture of acute hepatitis
Many cases of acute hepatitis pass asymptomatic
Symptomatic cases are similar to that of HAV
Acute HCV infection tends to be mild and insidious in onset unlike HBV
Extrahepatic manifestations due to circulating immune complexes; mainly in
HBV & HCV:
Serum sickness like prodrome marked by arthralgia or skin lesions e.g.
urticarial, purpuric, macular, or maculopapular rashes
Aplastic anemia
Glomerulonephritis
Vasculitis

Page | 285
Complications
1. Chronic carrier state
2. Chronic hepatitis
Risk:
Risk of chronic HBV infection is 90% in children younger than
1 yr; 30% for those 1-5 yr and 2% for adults
HCV is the commonest cause ever of chronic viral hepatitis
Complications
Cirrhosis & liver cell failure.
Hepatocellular Carcinoma
3. Acute Liver Failure (ALF); risk increases when there is coinfection or
superinfection with HDV and in an immunosuppressed host
4. Reactivation of chronic infection has been reported in immunosuppressed
children
Investigations
I. To prove acute hepatitis: As in HAV
II. For Etiology: Viral Markers
1. For HBV
Marker Significance
HBs Ag Acute infection; its rise closely coincides with the
onset of symptoms
If persist > 6 months o indicate chronic hepatitis
Anti HBc Ag IgM Acute infection; Reliable single marker later in the
acute phase as HBs Ag fall before the symptoms
disappear
Hbe Ag Acute infection ; a marker of active viral replication
and usually correlates with HBV DNA levels
HBe Ag positive mothers put very high risk of
perinatal transmission to their babies
Anti HBc Ag IgG Infection; recent or chronic
Anti HBs Ag If present alone, it indicate previous vaccination.
If present with anti-HBc Ag o resolved infections.
N.B. HBc – Ag is present only inside the hepatocytes.
Hbe – Ag is not structural antigen but it is produced by self-cleavage of the core antigen

Page | 286
2. For HCV and HDV

Detect specific RNA by PCR.
Detect specific antibodies.
N.B: Children born to HCV-infected womenĺ test for qualitative PCR in
infancy and anti-HCV after 12-18 mo of age
Prevention
1. Blood donation screening
2. HBV immunization
Combined: Both vaccine and immunoglobulin
A. Post exposure prophylaxis for infant born to HBs Ag + ve mothers
HBV immunoglobulin 0.5 ml IM, within 12 hr after birth plus the
first dose of HBV vaccine (which is given as 0, 1, 6)
Protective value of this regime is > 95%
Follow up: Post vaccination testing for HBsAg and anti-HBs should
be done at 9-18 mo:
Positive for anti-HBs ĺ The child is immune
If Positive for HBs Ag only ĺ The child is infected
Negative for both HBsAg and anti-+%VĺRepeat the vaccine
B. Post exposure in older child:
HBV immunoglobulin: 0.06 ml/kg within 24 hrs plus HBV vaccine
which given as 0, 1, 6
Active
HBV vaccine: (Recombivax HB and Engerix-B)
Nature: Recombinant DNA vaccine.
Time: 3 doses, IM at 0, 1, 6 months
Treatment
R As for HAV; Treatment of acute infection is largely supportive.
R Close monitoring for liver failure and extrahepatic morbidities is key
R Acute liver failure management include:
Referral to PICU in a center expert in liver transplant
Monitor vitals , conscious state and hepatic / renal chemistry
Fluid ,glucose, ammonia and electrolytes monitoring and correction
especially for hypophosphatemia (high phosphate is a bad sign)
Restrict or forbid proteins initially
Gastriprotection :proton pump inhibitors
Oral antibiotics (e.g. Neomycin) and Lactulose to sterilize the colon
Frequent enema preferably with lactulose
Correct coagulopathy by vit K, fresh frozen plasma or factor VIIa
In advanced cases with coma: Hepatic dialysis/transplantation

Page | 287
Chronic Hepatitis
Definition: An inflammatory process of the liver lasting longer than 6 months.

Recently o continuing hepatic inflammatory process manifested with severe
liver disease or features of chronicity (shorter time can be employed)
Chronic persistent hepatitis Chronic active hepatitis
Causes Auto immune o the commonest
Viral o HBV, HCV Viral o HBV, HCV, Delta virus.
Metabolic o e.g. Wilson disease.
Pathology - Erosions of the limiting plate.
- Inflammation limited to the portal zone - Piecemeal necrosis of hepatocytes.
- Little or no fibrosis. - If severe o bridging necrosis
- No cirrhosis. o fibrous septa
Clinical picture 1. Most cases have:
- Asymptomatic - Hepatosplenomegaly (HSM)
- May be non-specific: malaise, anorexia - Liver cell failure (LCF)
- May be tender hepatomegaly. 2. In auto immune; type there may be also:
- Iridocyclitis
- Thyroiditis
- Vasculitis o nephritis
- Serositis o arthritis , pleurisy
- Immune hemolytic anemia
- Clubbing
Complications Common:-Cirrhosiso portal hypertension
Very uncommon -Fulminate hepatic failure.
Investigations
1. Is it hepatitis? Yes. Yes
- ALT & AST o mild increase. o High (not alkaline phosphatase)
- Bilirubin o No or slight increase. o High. (2-10 mg/dl – mainly direct).
2. Is there liver decompensation? No Yes
- Albumin o Normal. o Low
- Prothrombine time o normal. o Prolonged
3. What is the cause?
- HBV & HCV markers. 1- Viral markers.
2- For auto immunity:
- Anit nuclear antibody (ANA).
- Anti – smooth muscle antibody.
- Anti liver kidney microsomal antibody
- Anti soluble liver antigen antibody.
- Elevated Ȗ-globulin levels
3- Metabolic assay.
- Liver biopsy o diagnostic

Page | 288
Treatment
1. Supportiveo As in acute hepatitis
2. Follow up o Clinical (for signs of decompensation) and laboratory.
3. Specific:
Auto immune hepatitis:
R Steroids 1-2 mg / kg /day till ALT & AST less than twice high normal
R Then taper slowly over 2-4 months to reach maintenance dose of 0.1 – 0.3
mg/kg/day
If steroids were poorly effective or have side effects
R Azathioprine is added with frequent monitoring for bone marrow

suppression
R Measurement of thiopurine methyltransferase activity before azathioprine
therapy is a predictive of myelotoxicity
Post viral:
HBV
Treatment is only indicated for patients in the immune active form of the
disease, as evidenced by elevated ALT and/or AST, who have fibrosis on
liver biopsy
Medications
Interferon-ĮE
Peginterferon-Į
Lamivudine
Adefovir
HCV
Medications approved by the FDA for use in children older than 3 yr of
age with HCV hepatitis
Interferon-ĮE
Peginterferon
Ribavirin
New therapies: direct-acting antivirals: Sofosbuvir and Simeprevir
4. Treat complications e.g.

Cirrhosis and fulminant hepatic failure o liver transplant

Page | 289
Reye’s syndrome
Definition
Acute mitochondrial encephalopathy with hepatic fatty degeneration
Clinical picture
Precipitated in a genetically susceptible person by the interaction of a viral
infection (influenza, varicella) and salicylate and or antiemetic use
Manifestations appear 5-7 days following viral infection
Acute hepatomegaly Acute rise of the intra cranial tension:

The patient remains anicteric Severe profound vomiting
Delirium and stupor
Generalized fits o coma
Eventual herniation is the main
cause of death
Diagnosis
Coagulopathy and elevated Cranial CT o Brain edema
aminotransferases, and CSF is normal but with raised
ammonia and hypoglycemia pressure (be cautious with lumbar
Liver biopsy o Fatty puncture)
infiltration and mitochondrial
damage
Reye like conditions with some inborn errors of metabolism e.g. Fatty acid
oxidation defects and valproate toxicity
Treatment
Largely supportive
Supportive care for acute liver failure
Coma care and reduction of raised intracranial tension


Page | 290
Wilson diseases
(Hepato lenticular degeneration)
AR defect in ceruloplasmin (Copper carrying protein) o Copper accumulate in:

Liver Forms of hepatic disease include
Asymptomatic hepatomegaly (± splenomegaly)
Subacute or chronic hepatitis
Acute hepatic failure
Cryptogenic cirrhosis, portal hypertension
Basal ganglia Intention tremor, dysarthria, rigid dystonia, chorea
Deterioration in school performance
Behavioral changes/ Psychiatric manifestations
Anemia Coombs-negative hemolytic anemia
Cornea Kayser Flisher ring
(absent in young patients)
Renal tubules Tubular defects (Fanconi like)
Diagnostic triad
- p Serum ceruloplasmin (< 20 mg/dL).
- n Urinary copper excretion after loading dose of D-penicillamine
- Liver biopsy o hepatic copper accumulation.
Screening
Family members of patients with proven cases require screening for
presymptomatic Wilson disease. Screening include determination of the serum
ceruloplasmin level and urinary copper excretion
Treatment
Restrict GLHWDU\FRSSHULQWDNHWRௗPJGD\
Copper chelating agent
D-penicillamine ௗPJNJGD\(penicillamine is an antimetabolite of
vitamin B6, additional amounts of this vitamin are necessary)
Alternative : triethylene tetramine dihydrochloride (trientine)
Adjuvant therapy: Oral zinc
Liver transplant

Page | 291
Liver Cirrhosis
Definition: Chronic liver disease with triad of:
- Hepatocytes necrosis.
- Regeneration nodules.
- Lost hepatic architecture.
Causes: - Post hepatitic.
- Metabolic: e.g. Wilson & hemochromatosis.
- Biliary: 1ry or 2ry to bile flow obstruction.
- Chronic hepatic congestion: cardiac cirrhosis.
Clinical picture
Compansated : Clinical picture of the cause.
Decompansated: Features of liver cell failure
1- Jaundice.
2- Bleeding tendency: - Skin bruises.
- GIT bleeding o Hematemesis & melena.
3- Ascites & generalized edema.
4- Hepatic encephalopathy:
- Due to increased ammonia and neurotoxins (false neurotransmitters).
- Manifested by: Disturbed sleep rhythm, flapping tremor, coma.
5- Hepato-renal syndrome: Functional renal failure in patients with end stage
liver disease due to intense renal vasoconstriction with systemic vasodilatation
o renal hypoperfusiono pre renal failure
6- Hepato pulmonary syndrome: - Intrapulmonary vascular dilatation o right
to left shunting of blood o hypoxemia, dyspnea, cyanosis & clubbing.
7- Others: - Feotor hepaticus.
- Palmar erythema.
- Spider nevi.
- Muscle wasting.
Diagnosis
1- To prove cirrhosis: - Abdominal ultrasound & MRI.
- Liver Biopsy o diagnostic (but avoided if decompensated)
2- For the cause: e.g. viral markers.
3- For complications:
- Liver functions tests o bilirubin, prothrombin time, albumin.
- Portal hypertension o see later.
Treatment
1- Supportive o Carbohydrates and vitamins rich diet
o Low salt diet (for cases with edema)
o Limit protein (for cases prone to encephalopathy)
2- Ant fibrotic: Colchicine.
3- Treatment of complications.
4- Liver transplant.

Page | 292
Ascites
Definition: Accumulation of fluid in peritoneal cavity.
Transudate Exudate Bloody Chylous
- Clear - Turbid Bloody with Milky white
- pproteins (<3gm/dl) - > 3 gm / dl RBCs on mic. ex.
- p Cells - n cells (PMNL)
- pSpecific gravity. - n (> 1018)
- No organisms. - may be organisms.
Causes: - Septic peritonitis - Trauma Rupture thoracic
1. Causes of generalized - T.B. peritonitis - Tumors duct due to trauma.
edema; cardiac, hepatic - Non microbial: - Bleeding disorders Or obstruction.
, renal x systemic lupus - Acute hemorrhagic
2. poly serositis x Metastasis pancreatitis
x B-cell lymphoma
Other causes: Bilious, urinary
Clinical diagnosis: see SHOTS clinical examination
Treatment of hepatic ascites:
1- Liver support (vitamins, avoids hepato toxic drugs, high carbohydrate diet).
2- Low salt and protein diet.
3- Diuretic: Aldactone.
4- Albumin or plasma infusion.
5- Therapeutic paracentesis provided:
- Tense ascites.
- Prothrombin concentration > 40%.
- Bilirubin < 10 mg/dl.
- Platelets > 40.000/mm3.
- Creatinine < 3 mg/dl.
- Aspirated volume not more than 20ml/kg/setting

Page | 293
Portal Hypertension
Definition: an elevation of portal pressure >10-ௗPPௗ+J (normal < 7 mmHg)
Causes:
Portal hypertension can result from obstruction to portal blood flow anywhere
along the course of the portal venous system
i. Extra hepatic portal hypertension:
Portal or splenic vein thrombosis due to:
Umbilical infection.
Neonatal sepsis.
Hypercoagulable states e.g. protein S & protein C deficiency.
Intra-abdominal infections
Inferior vena cava obstruction with e.g. constrictive pericarditis/
thrombosis
Congestive heart failure/tricuspid regurge
ii. Intra hepatic portal hypertension:
1. Pre sinusiodal ĺ - Chronic hepatitis.
ĺ - Schistosomiasis.
ĺ - Portal tract infiltrations
2. Sinusiodal ĺ - Cirrhosis (the commonest cause)
- Veno oculsive disease
3. Post sinusoidal ĺ - Budd-Chiari syndrome
(Nelson textbook of pediatrics 2016)
Clinical picture
Opened collaterals
Esophageal varices o hematemesis & melena(the commonest presentation)
Caput medusa
Hemorrhoids
Venous hum
Splenomegaly (the next most common presentation)
Ascites
Liver is
Shrunken in cirrhosis.
Enlarged tender in post sinusoidal causes
Normal in prehepatic causes.

Page | 294
Investigations
1- Abdominal ultrasound o for liver, spleen, ascites.
2- Measure portal vein pressure by ultrasound Doppler.
3- Upper GIT endoscopy for esophageal varices
4- Search for the cause.
Treatment
i. Emergency treatment (Control bleeding esophageal varices):
ABC
Take blood sample for investigation & ask for blood.
Order fresh blood transfusion
Fluid resuscitation followed by replacement of red blood cells
Correct coagulopathy by:
Vitamin K I.V
Fresh frozen plasma or platelets
Place nasogastric tube o to monitor ongoing bleeding.
H2-receptor blocker or proton pump inhibitor should be given
intravenously o reduce the risk of bleeding from gastric erosions
In most patients, particularly those with extrahepatic portal hypertension and

with normal hepatic synthetic function, bleeding usually stops spontaneously
With continued bleeding

Vasopression or Octreotide I.V infusion o p splanchnic flow.
Nitroglycerine skin patch decrease portal pressure and can ameliorate
some of its untoward effects of vasopressin
Endoscopic sclerotherapy with ethanol amine or much better band
ligation of varices.
With continued bleeding

Sengstaken – Blackmore tube o mechanical compression of
esophageal & gastric varices (this device is rarely used now)
ii. Prophylactic (Prevent subsequent bleeding):
Propranolol o p portal pressure
Porto-systemic Shunt operation
Trans jugular intrahepatic porto systemic shunt (TIPS) by an
interventional radiologist (problemĺPD\ precipitate hepatic
encephalopathy and is prone to thrombosis).
iii. Orthotopic liver transplantation

Page | 295
Gastrointestinal Bleeding
Causes
Upper GIT bleeding: Bleeding from above the ligament of Treitz:
a. Esophageal:
GERD
Varices
Tumors.
b. Gastric ulcers.
c. Duodenal ulcers.
Lower GIT bleeding: Bleeding below the ligament of Treitz:
Inflammatory bowel disease.
Intestinal obstruction (intussusception & volvulus
Meckel’s diverticulum.
Gastroenteritis.
Anal fissure.
Hemorrhagic blood disease:
Result in either upper or lower GIT bleeding e.g. hemophilia, purpura, DIC.
Management
1. Emergency treatment as (See bleeding esophageal varices).
2. Search for the cause:
a. History of: - Bleeding disorder// Liver disease.// Gastroenteritis.
b. Examination:
- Skin for o Signs of chronic liver disease.
o Signs of coagulopathy (e.g. purpura & Bruises)
- Abdominal o Hepatosplenomegaly (in chronic liver disease & leukemia)
o Distension (intestinal obstruction)
- P/R examination o For perianal ulcers & polyps.
c- Investigations:
- Rule out hemorrhagic blood diseases by o CBC
o Coagulation profile
o Liver function tests
- Abdominal X-ray and ultrasound o for obstructions & organomegaly.
- Stool analysis o For gastro enteritis & enterocolitis.
- Endoscopy o for varices, ulcers, polyps.
Treatment: of the cause
Medical e.g. for Hemorrhagic blood diseases, Gastro Enteritis
Interventional / Surgical e.g. for Varices, Polyps

Page | 296
Veno Occlusive Disease(VOD)

(Sinusoidal obstruction syndrome)
The most common cause of hepatic vein obstruction in children
Definition : Intrahepatic obstruction of hepatic veins.
Causes : After total body irradiation with or without cytotoxic drug
May be toxic injury by herbal teas or drugs
Clinical picture
Acute VOD Subacute VOD Chronic VOD
- Portal hypertension - Portal hypertension - Portal hypertension

- Hepatomegaly. - Hepatomegaly - Cirrhotic liver
- No splenomegaly. - Splenomegaly - Huge Splenomegaly
Diagnosis
1- As for portal hypertension
2- Liver biopsy o diagnostic.
Treatment
- Supportive
- In severe cases: liver transplantation
Budd Chiari Syndrome
Definition: Obstruction of the main hepatic veins.

Causes
Hypercoagulable states e.g. Polycythemia ,
Can complicate hepatic or metastatic neoplasms, collagen vascular disease,
infection, and trauma
Clinical picture
Acute stage Chronic stage.

- Acute hepatomegaly - Hepatomegaly.
- Acute abdominal pain & vomiting. - Portal hypertension.
- Acute ascites
Treatment
- Supportive
- In severe cases: liver transplantation

‫\‪(QGRFULQRORJ‬‬
‫‬
‫‬

Page | 297
Hypopituitarism
Definition
Underproduction of growth hormone (GH) alone or in combination with
deficiencies of other pituitary hormones
Physiology of growth hormone
GH is secreted form the anterior

pituitary in bursts (i.e. pulsatile
pattern)under control of hypothalamic
GH releasing hormone (GH. rH)
GH release is:
Stimulated by sleep, exercise and
hypoglycemia
Inhibited by somatostatin
Actions
Anabolic hormone especially on
long bones and muscles
Action is mediated by Insulin
Growth Factor 1 produced by the
liver:
Increase protein synthesis
Anti-insulin effect o lipolysis &
n blood glucose
Causes
i. Isolated growth hormone deficiency:
A. Genetic: due to
Mutation of growth hormone genes; AR, AD or XLR.
End organ resistance:
Defective GH receptors e.g. Laron syndrome
Post receptor GH insensitivity e.g. abnormal IGF gene or receptor
B. Acquired:
Idiopathic (The most common).
Post cranial irradiation (e.g. for leukemia).

Page | 298
ii- Multiple pituitary hormones deficiency:

A. Genetic:
Due to mutations of multiple pituitary hormones genes e.g. PROP1
Associations: May be optic nerve dysplasia (septo optic dysplasia).
B. Congenital:
Pituitary aplasia or hypoplasia.
Association: May be mid facial anomalies e.g cleft palate, solitary
maxillary central incisor
C. Acquired any lesion at hypothalamo- hypophyseal region:
Tumors e.g. Craniopharyngioma
Trauma
Infiltration e.g. histoiocytosis
Clinical picture
1. At birth:
Normal size (near normal weight and height)
Micropenis is a diagnostic clue.
May be neonatal emergency as apnea, cyanosis,
hypoglycemia
May be mid facial anomalies e.g. cleft lip & palate
2. Later on:
Normal intelligence
Severe growth failure
Proportionate short stature
Childish facies
Height below the 1st
Small face, nose &
percentile for age and sex
mandible
or height >2 SD below sex
Prominent forehead &
adjusted Mid-parent height
depressed nasal bridge
Growth velocity < 5cm/year
Wide anterior fontanel &
Appear by the end of the 2nd
fine hair
year Delayed teething
Micropenis in childhood; normal for body size in adults

Hypoglycemia: in infants and children; fasting symptoms in some adults
3. May be features of:

Septo optic dysplasia : nystagmus & visual impairment in infancy
Mid facial anomalies e.g. cleft lip / palate, solitary maxillary
central incisor
Increased intra cranial tension (in destructive lesions)
Associated hormonal deficiency e.g. hypothyroidism, diabetes insipidus

Page | 299
Investigations
1. Screen for GH deficiency
Low serum levels of IGF-1 and the GH-dependent IGF-Binding Protein 3
matched to normal values for skeletal age rather than chronological age
Normal values IGF-1 and IGF-Binding Protein 3 indicates GH deficiency
unlikely
2. Confirm GH deficiency
Measure peak levels of GH after provocative agents; insulin, clonidine, or
arginine or glucagon:
Normal peak levels of GH > 10 ng/ml
Low peak levels of GH (<10 ng/mL) GH deficiency
To confirm diagnosis 2 provocative tests should be done
In prepubertal children: A 3 days of estrogen priming should be used
before GH testing to achieve greater diagnostic specificity.
3. For associated deficiencies:
Measure other anterior pituitary hormones.
4. For the cause:
Skull CT & MRI for pituitary tumors, aplasia or hypoplasia
TRH stimulation test (differentiate between hypothalamic and
pituitary causes)
Random prolactin level: high in hypothalamic defects
5. For effect: Radiograph for delayed bone age
Treatment
1. Recombinant GH:
Dose: 0.18-0.3 mg/kg/week, divided into 6-7 daily subcutaneous
injections should be used as soon as GH deficiency is diagnosed
Criteria to stop therapy:
A decision by the patient that he or she is tall enough
A growth rate <1 inch/yr
And a bone age >14 yr in girls and >16 yr in boys
Concurrent treatment with a gonadotropin-releasing hormone (GnRH)
agonist to interrupt puberty will delay epiphyseal fusion and prolong
growth
Side effects of GH therapy:
A 6-fold increase in the risk for type 2 diabetes
Pseudotumor cerebri
Slipped femoral epiphysis
2. Recombinant IGF-1 for end organ unresponsiveness (e.g. Laron syndrome)

Page | 300
3. Treatment of other hormonal deficiency

4. For infants with micropenis:
One or two a 3-mo courses of monthly intramuscular injections of 25 mg of
testosterone enanthate can bring the penis to normal size
Puberty
Definition
It is a period of growth lasting 5 years, consisting of 3 stages and includes
physical, sexual & psychological changes.
Onset Girls: 8-13 years, Boys: 9-14 years
Sequence :
Girls Boys
- Breast development - Testicular growth
- Pubic hair - Pubic hair
- External genitalia maturation - Penis and scrotal growth
- Feminine habitus - Increased muscle bulk
- Axillary hair - Body hair (beard, axillary)
- Oil secretion and acne - Oil secretion and acne
- Menstruation - First seminal discharge.

Page | 301
Thyroid Gland
Thyroid gland secrete
Thyroid hormones:
Thyroxine (T4)
Triiodothyronine (T3) ; more potent than T4
Calcitonin (which deposit calcium salts in bone).
Functions of thyroid hormones
1- Normal maturation of the growing brain in the 1st year of life.
2- Normal skeletal growth.
3- Oxidative metabolism & energy production in all cells
Thyroid hormones synthesis
R Iodide transport (Trapping).
R Iodide is oxidized to iodine by thyroid peroxidase enzyme (organification).
R Iodination of tyrosine to form Mono & Di iodo tyrosine.
R Coupling of:
2 Di iodotyrosine o T4
Monoiodotyrosine & Di iodotyrosine o T3
R T3 & T4 are stored in thyroid gland as colloid (thyroglobulin).
R Only 20% of circulating T3 is produced by thyroid while 80% is produced by
peripheral conversion of T4 by deiodinase
Trapping
Iodide Iodide
Oxidation by peroxidase
Organic Iodine
Tyrosine
Mono /Di iodo tyrosine
Coupling
T3,T4 Store as thyroglobulin
Control of thyroid function:

Thyroid is regulated by pituitary thyroid stimulating hormone (TSH) in a
feedback mechanism.
TSH synthesis & release is controlled by hypothalamic TSH releasing hormone
(TRH).

Page | 302
Congenital hypothyroidism
Causes
A. Primary hypothyroidism:
1. Thyroid dysgenesis:
The commonest cause (85%).
Aplasia, hypoplasia or ectopic gland (may be lingual,
sublingual or subhyoid).
2. Defective thyroid hormone synthesis (Dyshormonogenesis):
The second common (15%)
Autosomal recessive disorders
Associated with goiter.
Examples:- Iodide transport defect.
- Organification defect: defective thyroid peroxidase enzyme
3. Transient hypothyroidism:
Trans placental passage of maternal anti thyroid drugs
Neonatal iodine containing antiseptics
4. Maternal iodine deficiency ĺEndemic goiter
5. End organ unresponsiveness to: - TSH.
- T3 & T4 (Pseudohypothyroidism).
B. Secondary hypothyroidism:
Due to TSH deficiency either: - Isolated or.
- With multiple pituitary deficiencies.
C. Tertiary hypothyroidism:
Due to TSH releasing hormone deficiency
Incidence: 1:4000; Female: male = 2:1.
Clinical picture
A. In neonatal period: there is may be
Prolonged physiologic Lethargy; cry little,
jaundice sleep much.
Poor feedingĺ chocking Widely open posterior
spells during feeding. and anterior fontanels
Subnormal temperature (Good initial clue)
Noisy breathing due to large May be heavier at Birth

tongue. May be Limbs and
Abdomen : constipation & genital edema
umbilical hernia
.
N.B: Most infants with congenital hypothyroidism are asymptomatic (due to Trans placental
maternal thyroxin ), so neonatal screening is mandatory

Page | 303
B. Full picture (by end of the 1st year): (cretinism)

* Delayed growth Short stature with persistent infantile proportions
* Delayed mental milestones
* Delayed motor milestones
* Physical features may include:
Head Neck
Coarse, brittle hair with low Short neck with supraclavicular pad
anterior hair line of fat
Delayed closure of anterior Thyroid is enlarged in
fontanel Endemic goiter.
Eyes are puffy, narrow palpebral Dyshormonogenesis
fissure Pseudohypothyroidism
Broad nose & depressed bridge Hoarse cry
Delayed teething
Thick large protruding tongue
Cardiac Limbs
Bradycardia Short broad hands
Pericardial effusion Generalized hypotonia
Cardiomegaly Occasional reversible
generalized
Abdomen pseudohypertrophy most
Protuberant prominent in calf (Kocher
Umbilical hernia Debre Semelaigne Syndrome)
Constipation
Genitalia Skin
Delayed maturation Cold & pale (resistant anemia)
Rarely precocious Dry (nmyxematous tissue)
puberty May be yellow (n carotene)

Page | 304
Investigations
1. Confirm diagnosis of hypothyroidism
Low serum free T4 (In hypothyroidism there’s compensatory increase in
peripheral conversion of T4 to T3; so measuring of T3 may be misleading)
Serum TSH
High in primary hypothyroidism
Low in secondary and tertiary hypothyroidism.
In pseudohypothyroidism T4, T3 and TSH all are high
2. For effect
Radiograph findings
(a) (b) (c)

Delayed bone age:
At birth o absent distal femoral epiphysis (in plane knee radiograph)
in 60% of cases (a)
Later o delayed appearance of ossific centers (by wrist x-ray)
Epiphyseal dysgenesis: multiple foci of ossification in heads of femur &
humerus (b)
Skull X-ray o Intrasutural (Wormian) bones (c) and large fontanels
Beaking of anterior part of T12 & L1 vertebrae.
Cardiac
ECG shows bradycardia and low voltage.
Echo / Chest x ray may show cardiac enlargement and effusion.
Others
High serum cholesterol/ Macrocytic anemia
3. For the cause
a. Thyroid scintigraphy (using radioactive 123I):
Absent uptake in:
Aplasia
Iodide trapping defect
Normal or increased uptake
in dyshormonogenesis.
Can localize ectopic thyroid.
Normal thyroid position Lingual thyroid in an infant

Page | 305
b. TRH stimulation test: (performed only with p TSH)

Differentiate between hypothalamic & pituitary defects
Give an i.v. bolus of TRH:
If T4 increases o hypothalamic defect i.e. Tertiary hypothyroidism
If T4 does not increase o pituitary defect i.e. Secondary hypothyroidism
c. Skull CT & MRI for pituitary tumors.
Treatment
Replacement therapy with sodium L-thyroxin (Eltroxin 50 μg tablet) for life
Dose: 10-15 μg/kg/day in neonate (start with the higher dose if T4 < 5 μg/dl)
6 - 8 μg/kg/d in infant
4 μg/kg/d in child
Follow up and monitoring
Clinical: for activity, milestones, growth and overtreatment
Lab: for T4 and TSH (done monthly in the first 6 mo of life, then
3 monthly)
Radiologic: monitor bone age
NB
x Overtreatment carries risk of craniosynstosis and temperament disorders
x To rule out transient hypothyroidism:
Discontinue treatment at 3 years for 3-4 weeks and test for TSH; it will
shoot in permanent hypothyroidism
This test is unnecessary in:
1. Infants with proven thyroid ectopia
2. In those who manifest elevated levels of TSH after 6-12 mo of therapy
because of poor compliance or an inadequate dose of T4
Prognosis
- Diagnosis & treatment before 3 months o normal linear growth and
intelligence
- Delay in diagnosis, failure to correct initial hypothyroxinemia rapidly,
inadequate treatment, and poor compliance in the first 2-3 yr of life result in
variable degrees of brain damage.
- Without treatment, affected infants are profoundly mentally deficient and
growth retarded
- As diagnosis of hypothyroidism is difficult in the first 3 months screening
for thyroid function (usually TSH) in all neonates is done in the first week
of the life

Page | 306
Acquired Hypothyroidism
Definition: Juvenile hypothyroidism with manifestations appearing after the 1 st
year.(After a period of normal thyroid function).
Causes
1. Thyroiditis
Autoimmune thyroiditis(Hashimoto disease; chronic lymphocytic thyroiditis):
The most common cause of thyroid disease in children and adolescents.
It is also the most common cause of acquired hypothyroidism, with or
without goiter
May be part of polyglandular auto immune syndromes ( associated with
e.g. DM, Addison)
Children with Down, Turner, and Klinefelter syndromes and celiac
disease or diabetes are at higher risk for associated autoimmune thyroid
disease
Suppurative.
Viral e.g. mumps.
2. Injury to thyroid o trauma, surgery, irradiation, cystinosis
3. Iodine containing drugs e.g. cough mixtures.
Clinical picture
Poor academic progress; but no mental retardation
Unexplained short stature
Skin: cold, pale(refractory anemia), excess myxoedematous tissue
Cold intolerance
Constipation
Delayed puberty (may be precocious).
Investigations
As before but
a. Search for auto antibodies for Hashimoto thyroiditis e.g.
R Thyroid antiperoxidase antibodies (TPO-Abs) and
Antithyroglobulin antibodies (anti-Tg Abs)
R TSH blocking antibody (may identify patients at future risk of
having babies with transient congenital hypothyroidism).
b. Check for associated auto immune disorders e.g. auto immune hepatitis,
diabetes mellitus, Celiac disease, Addison disease
Treatment:
Overt hypothyroidism (elevated TSH, low T4 or free T4), require
replacement treatment with levothyroxine
For subclinical hypothyroidism (elevated TSH, normal T4 or free T4),
many clinicians prefer to treat such children until growth and puberty
are complete, and then reevaluate their thyroid function

Page | 307
Causes of deafness & hypothyroidism

1- Pendred syndrome
Mutation in the chloride-iodide transport protein common to the thyroid
gland and the cochleao impaired iodide organification, & positive
perchlorate discharge test o Sensorineural deafness and Goitrous
hypothyroidism
2- Endemic goiter
3- Neglected hypothyroidism
4- Congenital rubella syndrome

Page | 308
Short Stature
Growth is strongly related to the genetic potential. A child's target height
(TH) is calculated by Mid Parent Height as follows:
R Girl = (height of mother in inches + height of father in inches)/2 - 2.5inches
R Boy = (height of mother in inches + height of father in inches)/2 + 2.5inches
Short stature is height below 3rd percentile for age and sex
Short stature is either:
Proportionate Disproportionate
- Upper segment/lower segment is - Upper segment/lower segment is abnormal
normal for age for age.
- Height equals span - Height does not equal span
I. Proportionate Short Stature
A. Normal types of short stature (about 90% of cases)
1. Familial (genetic) short stature
A short child who is growing close to his/her
target height percentile
Clues:
Small birth length (normal for the family)
Normal bone age and age of onset of puberty
Short parents (familial)
Short target height like their parents
2. Constitutional Growth Delay (CGD)

Growth is normal for the 1st 4-12 mo of life. Height is sustained at a lower
percentile during childhood with acceleration late in adolescence when their
peers stop growing leading to a final height that
is close to the target height
Clues:
Delayed bone and age of onset of puberty
Other family members (often one or both
parents) with histories of short stature in
childhood, delayed puberty, and eventual
normal stature
IGF-1 levels tend to be low for
chronological age but normal for bone age

Page | 309
B. Pathologic types:
n &KURQLFXQGHUQXWULWLRQĺmarasmus & nutritional dwarfism
o Chronic systemic disease
- Malabsorption syndrome e. g celiac disease, inflammatory bowel disease
- Chronic hemolytic anemia e.g. thalassemia
- Chronic renal failure, renal tubular acidosis, urinary tract infections.
- Chronic chest diseases e.g. cystic fibrosis, asthma
- Chronic heart diseases: congenital, rheumatic, cardiomyopathy
p Endocrinal causes:
- Hypothyroidism.
- Hypopituitarism.
- Hypercortisolism (Cushing syndrome) and adrenal insufficiency
- Precocious puberty
- Diabetes mellitus.
- Diabetes insipidus.
r Psychosocial dwarfism:
Due to maternal neglect or emotional deprivation
Evidence of functional hypopituitarism is indicated by low levels of
IGF-1 and suboptimal GH on provocation
History and careful observations reveal disturbed mother-child or
family relations
Associations: perverted or voracious appetites, enuresis, encopresis,
insomnia, crying spasms, and sudden tantrums
q Syndromes with short stature e.g.:
- Turner - Noonan
- Down - Other trisomis; e.g. 13 , 18
- Prader Willi - Silver Russell
s Intra uterine growth retardation: 10 –15% will be short.
II. Disproportionate Short Stature

A. With short limbs e.g.
- Achondroplasia
- Rickets
- Osteogenesis imperfecta
B. With short trunk e.g.
- Skeletal dysplasia e.g. Ectodermal dysplasia and Morquio s syndrome
- Fanconi anemia

Page | 310
Approach to Diagnosis
I. History
* Perinatal for:
Exposures; infections, maternal drugs
Birth weight and length (differentiate prenatal and postnatal causes)
Problems e. g microphallus & hypoglycemia in hypopituitarism.
* Past history suggestive of:
Chronic systemic disease.
Endocrinal disorder
* Dietetic history for under nutrition or eating disorders.
* Family history for parent’s height, other short siblings and social problems
II. Examination
Clinical tests
Check parent’s KHLJKWĺWRUXOHRXWJHQHWLFFDXVHV
'HWHUPLQHW\SHRIVKRUWVWDWXUHĺSURSRUWLRQDWHRUGLVSURSRUWLRQDWH
Plot patient weight and height on growth charts:
1. Short stature following own growth curve:
a. Familial short stature
b. Constitutional growth delay
2. Short stature with decelerating growth pattern
Weight for age < height for age Weight for age > height for age
- Chronic systemic disease - Endocrinopathy e.g. Hypothyroidism
- Chronic undernutrition Cushing , Hypopituitarism
- Cardiac disease - Syndromes
- Skeletal dysplasia
3. Short stature with normal weight for height: Emotional deprivation
Clinical examination
Evaluate nutritional state: check for muscle wasting, subcutaneous fat
loss and signs of vitamin deficiencies.
Complete systemic examination: including cardiac, chest, abdomen,
neurologic
Check for features suggesting endocrinal disorders e.g. hypothyroidism.
Check for dysmorphic features e.g. Down, Turner
III. Investigations
Assess bone age by left wrist X-ray:
Normal in familial short stature
Delayed in most other causes

Page | 311
Search for systemic diseases by:

8ULQHDQDO\VLVĺIRUJOXFRVXULD87,RVPRODOLW\
6WRRODQDO\VLVĺfor malabsorption
CBC ĺIRUDQHPLD
(65ĺLQFUHDVHGLQLQIHFWLRQ LQIODPPDWLRQ
Urea, creatinine ĺfor renal failure
Chest X-ray ĺIRUVXVSHFWHGFKHVWGLVHDVH
(FKRFDUGLRJUDSK\ĺIRUVXVSected cardiac defect
Serum pH, calcium, phosphate for metabolic bone disease
Specific e.g. Celiac screen, malabsorption workup, chromosomal
studies
3. Hormonal assay:
Free T4 & TSH for hypothyroidism (Because thyroid hormone is
necessary for normal GH synthesis, it must always be assessed before GH
evaluation)
Provocative growth hormone level & IGF-1 for hypopituitirsm
Night time blood or salivary cortisole level for Cushing
Blood glucose for diabetes
Serum &urine osmolality for diabetes insipidus
Treatment
1. Treat the cause e.g.
Gluten free diet for celiac
EL-troxin for hypothyroid
2. Recombinant growth hormone
“FDA approved indications of GH therapy”:
GH deficiency
Turner syndrome
Chronic renal failure before transplantation
Idiopathic short stature
Small-for-gestational age short stature
Prader-Willi syndrome
Noonan syndrome
3. Adequate balanced diet
4. Psychologic support

Page | 312
Diabetes Mellitus
Definition:
Chronic, metabolic syndrome characterized by hyperglycemia as a cardinal
biochemical feature
Deficiency of insulin or its action with subsequent defect in metabolism of
carbohydrates, protein & lipids
Actions of insulin
p Blood glucose by o n Glucose uptake by cells
o p Gluconeogensis
o p Glycongenolysis
n Lipogenesis
Anabolic effect
Types of diabetes mellitus
1. Insulin dependent (Type 1 DM)
2. Non-insulin dependent (Type 2 DM)
3. Secondary diabetes mellitus:
Endocrinopathies: Cushing disease, Hyperthyroidism, Acromegaly
Drug- or chemical-induced: Steroids, Thyroid hormone
Diseases of the exocrine pancreas: Hemochromatosis, Cystic fibrosis,
Pancreatitis
Criteria for diagnosis
Fasting plasma glucose 2-hr plasma glucose
during the OGTT
x Diabetes mellitus mg/dL 200 mg/dL
(7.0 mmol/L)
x Impaired glucose tolerance 100-125 mg/dL 140 mg/dL, but
< 200 mg/dL
OGTT: Oral Glucose Tolerance Test, Values in mg/dl

Page | 313
Insulin dependent diabetes mellitus

Etiology
ȕ-cell destruction leading to absolute insulin deficiency, may be related to:
Genetic predisposition: associated with HLA -DR3, DR4
Auto immune response (Humoral & cell mediated response against islet cells):
Evidence:
Presence of Islet cell autoantibodies
Association with other auto immune diseases e.g. thyroiditis
Environmental factors:
Viral infection e.g.: mumps, rubella, measles, EBV
Pathogenesis
Insulin deficiency results in disturbance of carbohydrate, fat & protein
metabolism.
x Fat metabolism: p Lipogenesis o n free fatty acids ( FFA) on Ketone bodies
x Carbohydrate metabolism:
- Hyperglycemia due to - p glucose uptake & utilization by the cells
- n gluconeogenesis & glycogenolysis
- Hyperglycemia leads to osmotic diuresis o polyuria & polydipsia
x Protein metabolism: n proteolysis o p body weight.
Clinical picture
R Polyuria, polydipsia, polyphagia & weight loss.
R Diabetic keto-acidosis (DKA) is the presenting feature in 25% of cases
(10% in T2DM).
R Secondary nocturnal enuresis
Diagnosis of diabetes mellitus
Symptoms of diabetes mellitus (include polyuria, polydipsia, and
unexplained weight loss with glucosuria and ketonuria ) plus
random plasma glucose 200 mg/dL (11.1 mmol/L)
or
Fasting (at least 8 hr) plasma JOXFRVH mg/dL (7.0 mmol/L)
or
2-hr plasma glucose during the OGTT mg/dL
or
Hemoglobin A1C 6.5% (Results should be confirmed by repeat testing
if in absence of unequivocal hyperglycemia)
(Nelson textbook of pediatrics 2016)

Page | 314
Diabetic Keto Acidosis (DKA)
Definition
Metabolic disorders due to acute insulin insufficiency
Risk Factors:
Omission of insulin dose by error or during inter current illness
Insulin pump failure
Adolescent girls
Psychiatric disorders including eating disorders
Previous DKA
Pathogenesis
History of exposure of diabetic patient to stresses (e.g. infection, trauma, and psychic).
Acute insulin insufficiency
Hyperglycemia nn FFA
Ketonemia nn ketone bodies.
Osmotic Aceto acetic acid & acetone

diuresis B (OH) Bytric acid
Metabolic acidosis acetone odor of breath
Polyuria ketonuria Acute abdominal pain Rapid & deep breathing

& vomiting (Kussmaul breathing)
Dehydration
Along with metabolic acidosis coma
Clinical stages of DKA
Early Then Later

Polyuria Dehydration Progressive obtundation
Nausea and vomiting Rapid, deep, sighing Impaired consciousness
Abdominal pain mimicking (Kussmaul)breathing
an acute abdomen

Page | 315
Diagnosis
Diagnostic criteria of DKA
Diabetic ĺ+\SHUJO\FHPLDEORRGJOXFRVH>200 mg/dL [§11 mmol/L]
Keto ĺ.HWRQHPLDDQGNHWRQXULD
Acidosis ĺ9HQRXVS+<7.3 and/or bicarbonate <15 mmol/L
Severity of DKA
Mild Venous pH 7.25-7.35 Or Bicarbonate 16-20 mmol/L
Clinical: Oriented, alert but fatigued
Moderate Venous pH 7.15-7.25 Or Bicarbonate 10-15 mmol/L
Clinical: Kussmaul respirations; oriented but sleepy; arousable
Severe Venous pH <7.15 Or Bicarbonate <10 mmol/L
Clinical: Kussmaul or depressed respirations; depressed sensorium
to coma
Management
Assess
Severity of dehydration (most cases are considered 5- 8% dehydrated)
Level of consciousness using Glasgow coma scale
Request
Plasma glucose, HbA1c, urinalysis for ketones, blood ß-
hydroxybutyrate and venous pH
Electrolytes, blood urea nitrogen, creatinine, calcium, phosphorus, and
magnesium concentrations
CBC and cultures (blood, urine) if infection is suggested
ECG for baseline evaluation of potassium status
A. Acidotic phase (in ICU)

DKA is a medical emergency that should follow ABC scheme
Admit to the ICU
Airway Secure the airway
Insert airway in comatose
Insert nasogastric tube if conscious level depressed
or the child is vomiting
100% O2 for hypoxia
Breathing ± intubation and ventilation
Circulation Site 3 IV lines one for I.V fluids , a 2nd for I.V
insulin and a 3rd sampling cannula
Obtain blood sample for investigations
Give antibiotics to febrile patients

Page | 316
Monitoring using flow sheet

Hourly Two hourly lab tests for the first 12 hours
Vital signs Glucose
Neurologic state for warning signs of Blood gases
cerebral edema and Glasgow coma Blood ß-hydroxybutyrate
scale if comatose Serum electrolytes
Cardiac monitor for potassium status Blood urea nitrogen
Capillary blood glucose Calcium, magnesium, phosphorus
Amount of insulin
Fluid input and output (catheter)
Urine ketones until cleared Weigh the patient twice a day
1. Fluid therapy
Shock therapy
- 10 ml/kg over 1 hour can be repeated up to 30 ml /kg
- 0.9% saline or lactated ringer
In the 2nd hour after the shock therapy and until resolution of DKA:
Fluid requirement = Fluid maintenance + Fluid deficit (85 ml/kg) – Boluses
fluids given over next 23 hour (36 hours in severe cases)
N.B
Fluid deficit = % Dehydration × Body weight
Fluid maintenance (24hr) = 100ml/kg(for the 1st 10 kg) + 50ml/kg (for the 2nd
10) + 25 ml/kg (for all remaining kg)
Replace any ongoing fluid loss in vomiting or diarrhea or massive polyuria
Type of fluid
0.45% NaCl plus 20 mEq/L K phosphate and 20 mEq/L K acetate
If K <3 mEq/L, give 0.5 to 1.0 mEq/kg as oral K solution OR increase IV K to
80 mEq/L
Bicarbonate therapy is rarely necessary and may even increase the risk of
hypokalemia and cerebral edema
2. Insulin therapy
Use regular insulin (e.g. Actrapid)
Slow infusion 0.1 unit/kg/hour without bolus must be given at the
beginning of therapy
Prepared by adding 50 units (0.5 ml) soluble insulin to 49.5 ml 0.9%
saline in 50 ml syringe pump to provide 1unit/ml concentration and
insulin started at 0.1ml/kg/hour

Page | 317
Precautions with insulin therapy

If the blood glucose concentration drops too quickly before the DKA has
resolved:
x Serum glucose has decreased < 300 mg/dL ĺGlucose is added as a
5% solution
x Serum glucose has decreased < 200 mg/dLĺGlucose is added as a
10% solution
x If the serum glucose falls further despite these interventions, ĺThe
insulin infusion can also be lowered to 0.05 U/kg/hr
Aim to keep blood glucose at about 11 mmol/L (200 mg/dL) until

resolution of DKA
Shift to to oral intake and subcutaneous insulin
9 When DKA has resolved indicated by:
Bicarbonate >15 mEq/L; pH >7.30
Sodium stable between 135 and 145 mEq/L
No emesis
9 Subcutaneous insulin
Dose: 0.2- 0.4 u/kg every 6-8 hr
To prevent rebound hyperglycemia the first injection should be
given 30 minutes before stopping the insulin infusion
3. Treat precipitating factors e.g. Antibiotics for infections.
Hazards during treatment of DKA
1. Cerebral edema
Warning clue
Serum sodium should increase by about 1.6 mmol/L for each 100 mg/dL
decline in the glucose; the sodium should steadily increase with therapy.
Declining sodium may indicate excessive free water accumulation and the
risk of cerebral edema
Signs of cerebral edema
R Headache & slowing of heart rate
R Change in neurological status
(restlessness, irritability, increased
drowsiness, incontinence)
R Specific neurological signs (e.g., cranial nerve palsies)
R Rising blood pressure
R Decreased O2 saturation

Page | 318
Treatment
Initiate treatment as soon as the condition is suspected.
Reduce the rate of fluid administration by one-third.
Give mannitol 0.5–1 g/kg IV over 20 minutes and repeat if there is no
initial response in 30 minutes to 2 hours
Hypertonic saline (3%), 5–10 mL/kg over 30 minutes, may be an
alternative to mannitol or a second line of therapy if there is no initial
response to mannitol
Elevate the head of the bed
Intubation may be necessary for the patient with impending
respiratory failure
1. Hypokalemia.
2. Severe hypophosphatemia
3. Hypoglycemia
Hint: “I myself prefer adopting the British Society of Paediatric Endocrinology
and Diabetes protocol for DKA, 2015. It is very easy and less complicated.
Please google it” Mohamed El Koumi
Mortality rate of DKA: About 0.2% due to:
Cerebral edema accounts for 60% to 90% of all DKA deaths
Hypokalemia induced arrhythmias
Sepsis / aspiration pneumonia
Differential diagnosis: From other causes of coma in diabetic child:
A. Hyperosmolar non ketotic coma (Hyperglycemic hyperosmolar state;HHS)
Plasma glucose concentration >33.3 mmol/L (600 mg/dL)
Arterial pH >7.30
Serum bicarbonate >15 mmol/L
Small ketonuria, absent to mild ketonemia
Effective serum osmolality >320 mOsm/kg
Clinically : Stupor or coma, severe dehydration
B. Hypoglycemic coma
History :
Known diabetic with insulin overdose or exercise or delayed meals
Clinically
Reactive sympathetic stimulation (ĹFDWHFKRODPLQHV Pallor, hunger
pains, tachycardia, sweating, jitterness, tremor, irritability
Glucopenia of CNS: Lethargy, limpness, may be seizures.
Blood glucose < 50 mg/dl (< 2.6 m mol /l)
Rapid response to I.V. glucose

Page | 319
B. Post acidotic phase

Regular Insulin Diet
Dose: 0.2-0.4 u/kg/ 6-8 hrs; SC Seek dietitian advice
Given 0.5 -1 hr before meals Sips of water
Increase or decrease insulin dose Skimmed milk
by 10% to keep blood glucose Dietetic juice
between 100-180 mg/dl Two days later give average diet
C. Lifelong management
1. Insulin
Starting Doses of Insulin (units/kg/day)
No DKA Post DKA
Prepubertal 0.25-0.50 0.75-1.0
Pubertal 0.50-0.75 1.0-1.2
Postpubertal 0.25-0.50 0.75-1.0
Types
Short acting
Regular insulin (Crystalline insulin, Humulin R)
Ultra short acting: Insulin Aspart ( Novorapid ) / Lispro ( Humalog )
Intermediate insulin (NPH, insulin Monotard , Humulin N)
Long acting insulin (Glargine ; Lantus and Detemir)
Regimens
1. Multiple dose injections (recent, very effective):
Use Glargine or Detemir as basal insulin at bed time
The basal insulin should be 25-30% of the total dose in toddlers and
40-50% in older children
The remaining insulin is given as pre meals boluses of ultra-short
acting analogs (usually Novorapid or Humalog) based on carbohydrate
in meals
2. Two injections regimen:
2/3 the total daily dose before breakfast
1/3 the dose before evening meal
Each dose contain 1/3 short acting analog & 2/3 NPH
3. Three injection regimen:
NPH and short acting analog bolus at breakfast
Short acting analog bolus alone before afternoon snack or the main
evening meal
NPH at bed time
4. Continuous subcutaneous insulin infusion using automated insulin pump

Page | 320
Adjustment:
Increase or decrease insulin dose by 10% to keep blood glucose:
Pre meal 70-145 mg/dl
Post prandial (1-2 hours) < 180 mg/dl
Pre bed time 125-180 mg/dl
2. Instructions
Diet o 3 main meals with 2 snacks (engage a dietician expert in diabetics
diets).
In infections increase rapid acting insulin by 10%
Decrease insulin before exercise
3. Monitor
a. Daily blood glucose at least 4 times
Before breakfast, lunch, supper& at bed time.
Initially test blood glucose also between 12AM & 3AM.to exclude nocturnal
hypoglycemia
b. Glycosylated hemoglobin (Hb A1C).
Fraction of hemoglobin to which glucose has been attached.
Measured as a percent of total hemoglobin.
Value: Reflect average blood glucose over previous 2-3 months:
Normal, non-diabetic o < 6%
American diabetes association recommends:
Hb A1C of <8.5 % in toddlers
Hb A1C of < 8 % in children
Hb A1C of < 7.5 % in teenagers
Honey moon period
* Due to residual E-cell function o release insulin so About 75% of new
diabetics complain recurrent hypoglycemia which may recur for weeks to
months.
* Advice: Never stop insulin but reduce the dose to avoid hypoglycemia.
Somogi phenomenon
* Due to large insulin dose > 2 u/kg/d o Late nocturnal hypoglycemia occur o nn
anti insulin hormones o early morning hyperglycemia.
* Advice: Reduce the evening intermediate insulin by 10%
Dawn phenomenon
* Due to overnight growth hormone secretion o antagonise insulin action o
early morning hyperglycamia.
* Advice: Increase the evening intermediate insulin by 10%

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Polyuria

Definition: Passage of excessive urine output > 2 liters/m2
Causes
Endocrinal Renal Psychogenic
* Diabetes mellitus * Hypokalaemia (<2.5 meq/l). * Compulsory water
* Diabetes inspidus * Renal tubular acidosis ingestion
* Barttar syndrome
* Hypercalcemia (> 13 mg/dl).
* Chronic renal failure.
Diabetes Insipidus
Definition
Inability to produce concentrated urine due to either
1. Decrease ADH production Neurogenic diabetes insipidus.
2. Lack of response of renal tubules to ADH nephrogenic diabetes insipidus.
Clinical picture
i- Polyuria = Urine output : 4-10 Liter/day.
- Polydipsia (Irritable infants)
- 2ry nocturnal enuresis.
- If water inaccessible o Dehydration
o Electroyte disturbance.
o Fever (no sweating).
o Shock in severe cases.
ii- Growth retardation
iii- May be features of the cause e.g n ICT in craniopharyngioma
Investigations
1. Urine:
- Specific gravity: 1002-1005 (diluted)
- Osmolality: low (50-200 m.osmol/L)
- No pathological constituents
2. Plasma osmolality: High (> 295 m.osmol /L)
3. Water deprivation test.
4. Vasopression stimulation test
Treatment
i Neurogenic o Desmopressin intranasal twice daily
i Nephrogenic o Adequate hydration.
o Correct hypokalemia by:
- Oral potassium.
- Potassium sparing diuretics.
o Indomethacin .

‫‪Neurology‬‬
Page | 322
Meningitis
Definition: Inflammation of the membranes covering the brain & spinal cord.
Types: - Bacterial
- Aspetic e.g. viral, fungal
- Tuberculous
Bacterial (Septic) meningitis
Causes
G –ve bacteria G +ve bacteria
Cocci x Nisseria meningitides type x Pneumococci ++ in infants
A, B, C, D, Y, W 135** x Staphylococci & children
x Streptococci
++ in neonates
Bacilli x E.coli x Listeria monocytogenes
x Hemophilus influenza.
N.B. ** Serogroup B is responsible for more than 50% of cases in children less than 1 year and
has also been associated with outbreaks on college campuses
Transmission: - Droplet infection mostly (Blood borne in neonatal sepsis)
Clinical picture
1. Non specific
High fever (may be hypothermia in neonates).
Poor feeding
Rose spots may appear on the trunk & extremities in meningeococcal
septicemia.
2. Features of increased intracranial pressure (ICP)
Before fontanel closure o tense, bulging anterior fontanel
After closure of fontanels:
Severe bursting headache (irritability)
Blur of vision
Projectile vomiting (in the morning, not preceded by nausea)
Cushing response (hypertension & bradycardia)
3. Features of meningeal irritation: (less sensitive in infants)
Neck rigidity (stiffness) o limited neck flexion
Opisthotonus o arched back
Kernig’s sign o inability to extend the leg after the thigh is flexed to a
right angle with the axis of the trunk.
Brudzinski leg sign: Passive flexion of one hip o flexion of the other hip
and knee
Brudzinski neck sign: Passive flexion of the neck o flexion of the hip &
knee.

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4. Neurologic signs
Stupor & drowsiness
Convulsions o usually generalized
Coma
Clinical types
1- Meningitic form o the classic presentation as before.
2- Fulminant meningitis.
- Abrupt fever.
- Severe headache and convulsions.
- Rapidly progress to coma.
- Fatal within 48 hrs.
3- Septicemic form (usually complicating meningeococcal form)
- Very bad general condition
- Shock
- Purpura & ecchymosis
- Meningitis develop within 1-2 days (or not at all)
Complications
1- Syndrome of inappropriate secretion of antidiuritic hormone (SIADH) o so,
maintenance fluids must be at 2/3 normal to avoid brain edema.
2- Neurologic complications:
- Increased intracranial pressure (ICP) o May leads to cerebral or
cerebellar herniation
- Subdural effusion
- Cranial nerve lesions (commonly oculomotor, 6th & 8th nerves).
- Hydrocephalus.
3- Peripheral circulatory complications
i- Waterhouse Friedrichson syndrome
- Septicemia
- Shock
- Extensive purpura
- Adrenal hemorrhage
(acute adrenal failure).
ii- DIC: Gangrenous patches & extremities
4- Dissemination of infection: endocarditis, arthritis , osteomyelitis
Investigations
1. CBC o /HXNRF\WRVLV ĹĹ301/
2. Blood culture reveals the responsible bacteria in up to 80-90% of cases

Page | 324
3. C-reactive protein, ESR, and procalcitonin have been used to differentiate

bacterial (usually elevated) from viral causes of meningitis
4. Lumbar puncture (LP) & CSF examinations:
Value
Diagnostic (Discover organismĹ301/Ĺ3URWHLQĻ*OXFose)
Determine appropriate antibiotics by culture & sensitivity.
Evaluate treatment: CSF become sterile within 24- 48 hours of
appropriate antibiotics
Contraindications for an immediate LP
1. Evidence of increased ICP (other than a bulging fontanel), such as 3rd
or 6th cranial nerve palsy with a depressed level of consciousness, or
hypertension and bradycardia with respiratory abnormalities
2. Severe cardiopulmonary compromise requiring prompt resuscitative
measures for shock
3. Infection of the skin overlying the site of the LP
What to do if an LP is delayed?
Initiate empirical antibiotic therapy
CT scanning for evidence of a brain abscess or increased ICP
LP may be performed after increased ICP has been treated
Condition Appearance Pressure Protein Glucose Leukocytes / ml Organism
(mmH2o) (mg/dl) (mg/dl)
Normal
Clear 50 - 80 5 – 20 40-80 0-5 (monocytes) Nil
CSF
Bacterial Turbid nn nn pp nn (100-60.000) +ve Gram stain*
meningitis (> 100) Mainly PMNLs +ve culture
TB Web nn nn pp n (10-500) Acid fast bacilli
meningitis On stand (> 100) Early PMNLs by zehl nelsen
then lymphocytes stain.
Viral Clear Normal Mild n Normal n (10-500) Viruses may be
meningitis or (< 100) or pp Early PMNLs isolated
slightly n later mononuclear
cells predominate
* Gram stain is positive in 70-90% of patients with untreated bacterial meningitis

N.B: In partially treated meningitis
9 Culture and gram stain are usually negative
9 But Pleocytosis with a predominance of neutrophils, elevated protein level,
and a reduced CSF glucose usually persist for several days

Page | 325
1- From other causes of meningitis
2- Meningism:
- Noninfectious meningeal irritation due to extra cranial lesions
- Causes: Upper lobe pneumonia, otitis media, shigellosis
- CSF is normal
3- Brain abscess
4- Encephalitis
Management
A. Treatment
1. Antibiotic therapy
Parenteral antibiotics according to culture and sensitivity for 2- 4 weeks
Empirical therapy while waiting for culture results:
9 Third-generation cephalosporins (cefotaxime 300mg/kg/day
divided 6 hourly or ceftriaxone 100mg/kg/day)
Plus
9 Vancomycin ௗPJNJௗKUJLYHQHYHU\ௗKU
9 If a patient is immunocompromised and Gram-negative bacterial
meningitis is suspected, initial therapy might include ceftazidime
and an aminoglycoside or meropenem
9 If Listeria monocytogenes infection is suspected, as in young
infants ,give DPSLFLOOLQ ௗPJNJௗKUJLYHQHYHU\ௗKU
2. Supportive therapy (Nelson 2016)

Measures to p ICP
- Mannitol 0.5 –1gm/kg iv
- Furosemide 1mg/kg iv
Corticosteroids
Indications:
a. H. influenza meningitis:
Value: Reduce inflammatory response caused by cell lysis
Use dexamethasone 0.15 mg/kg/dose every 6 hours for 2 days
Maximum benefit if given 1-ௗKUEHIRUHDQWLELRWLFVDUHLQLWLDWHG
b. Septic shock to improve general condition.
c. Adrenal failure
Treatment of complications e.g. convulsions
- Immediate relief by diazepam or lorazepam
- Then phenytoin loading and maintenance

Page | 326
B. Prevention
Isolation of the case
Vaccination against H.influenza, meningococci, pneumococci
Chemoprophylaxis for contacts: e.g. rifampicin 10-20 mg/k/day for 2-4
days.
Prognosis Depends on:
1- Age: the younger the age, the worse the prognosis.
2- Course: fulminant meningitis has worse prognosis.
3- Cause: - E.coli & staph on fatality & n long term sequalae.
- H.influenza & pneumococci o moderate prognosis.
- Meningococci o < 5% fatality & no residual disability.

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Aseptic meningitis
Meningitis with no micro organisms detected in CSF by gram stain or bacterial

culture.
Causes: - Mostly viral o Herpes simplex virus
o Enteroviruses (Echo & coxachie)
o Mumps
o Ebstein barr virus
- Protozoa o Malaria
o Toxoplasma
- Non infectious o CNS leukemia
o Intrathecal injection
o Post vaccination.
Diagnosis: - CSF analysis
- Viral isolation
Treatment: - Supportive ± antiviral.

Page | 328
Seizures
Definition:
A seizure is
Transient , paroxysmal, time limited, involuntary disturbance of brain
function
Manifested by abnormal motor, sensory, behavioral or autonomic
activities
With or without impaired consciousness
Causes
A. Acute Seizure
1. Febrile Seizure
2. First epileptic fit.
3. Symptomatic seizures
CNS causes:
- Infection o meningitis, encephalitis, brain abscess.
- Irritation o brain edema
- Tumors of the brain
- Toxic o tetanus, drug (e.g aminophylline), lead encephalopathy
- Hemorrhage o trauma, hemorrhagic blood diseases.
- Hypoxia o hypoxic ischaemic encephalopathy.
- Hypertensive encephalopathy.
Metabolic causes:
- Bilirubin encephalopathy
- Uremic encephalopathy
- Hepatic encephalopathy
- Hypo (glycemia, calcemia, magnesemia)
- Hypo or hypernatremia.
- Pyridoxine (B6) deficiency
- Inborn errors of metabolism
B. Recurrent Seizures
1. Epilepsy
2. Symptomatic seizures
Tetany
Degenerative brain diseases
Chronic metabolic causes
- Inborn errors of metabolism
- Hepatic /Uremic encephalopathy

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Febrile Seizures
Definition: Seizures in age vulnerable children due to:
- Rapid rise of body temperature.
- Due to extra cranial causes (mostly viral)
Incidence: - Affect 4% of children.
- Family history in about 20 % of cases (genetic base do exist)
- Recurrent in 30-50% of cases specially in those with family history
Diagnostic criteria
1. Age: 6 - 60 months (convulsions below or above this age is not febrile)
2. Fits occur within 8-12hrs from onset of fever.
3. No evidence of CNS infection (e.g. meningitis), nor metabolic disease
4. Evidence of extra cranial infection (e.g. tonsillitis, otitis media, roseola)
5. Occur in the absence of a history of prior afebrile seizures
6. Type of convulsions:
Simple (Typical) Complex
- Generalized tonic-clonic. - Focal
- Last < 15 min. - Last > 15 min
- One fit only in the same illness. - Recurring within 24 hr
- The commonest form - Uncommon.
Investigations
1. Lumbar puncture to rule out meningitis
Mandatory in
Infants below 6 months presenting with fever and seizures
Ill looking children
Clinical suspicion of meningitis
Optional in
Children 6-12 months not vaccinated for Haemophilus influenzae type
b & Streptococcus pneumonia or immunization status is unknown
Children who have been pretreated with antibiotics
2. EEG and Neuro imaging (CT, MRI)
Only for cases with high risk of epilepsy ; usually not required for 1st
simple febrile seizure
EEG is done > 2 weeks of the attack
Risk of subsequent epilepsy is higher with:
Neurodevelopmental abnormalities
Complex febrile seizures (focal)
Family history of epilepsy
3. Blood tests e.g. electrolytes, blood glucose if clinically indicated

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N.B: Major risk factors predicting recurrence of febrile seizures:

Age <1 yr
Duration of fever < 24 hr
Fever 38-39 °C
1. Intracranial infections: Meningitis, meningeo encephalitis, and brain abscess
2. Epileptic fit precipitated by associated fever
3. Epilepsy syndromes typically start with febrile seizures e.g.
Generalized epilepsy with febrile seizures plus (GEFS+) : multiple
febrile seizures and several types of afebrile generalized seizures
Severe myoclonic epilepsy of infancy (Dravet syndrome): seizures
starts febrile then become afebrile with evolving developmental delay
Treatment
In general, antiepileptic therapy, continuous or intermittent, is not
recommended for children with one or more simple febrile seizures
1. Acute care of febrile seizure attack:
x Full history and thorough examination
x Fever control by paracetamol and tepid sponges or cold bath.
x Fit lasting more than 5 minuteso Diazepam, lorazepam, or midazolam
x Investigate and treat the underlying cause
x Treatment of febrile status epilepticus
2. Parent education about:
x Acute handling of seizures at home
x Seizures lasting > 5 minutes o rectal diazepam or buccal or intranasal
midazolam
x Fever controlo reduce the discomfort not the seizure recurrence
x During fever o intermittent oral diazepam 0.3 mg/kg q8 hours or
rectal diazepam (0.5 mg/kg as a rectal suppository every 8 hr), reduce,
but do not eliminate, the risks of recurrence of febrile seizures
(Nelson 2016)

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Epilepsy
Epilepsy is
A brain disorder with predisposition to generate seizures with neurobiologic,
cognitive, psychologic, and social consequences of this condition
It is considered to be present when
2 or more unprovoked seizures occur in a time frame of longer than 24 hr
Or
At least 1 unprovoked epileptic seizure with enough EEG and clinical
information to demonstrate recurrences
(Nelson 2016)
Causes
1. Idiopathic (Now termed genetic) in 80% of cases
2. Organic (secondary) in less than 20% of cases
- Congenital cerebral malformation.
- Degenerative brain diseases.
- Post-traumatic, post-hemorrhagic, post-infection, post-toxic, post-anoxic
Classification
A. Focal (partial) seizures
* Only one part of the body is involved i.e. focal.
* Types:
1. Focal seizures without impairment 2. Focal seizures with impairment of
of consciousness (Simple partial seizures) consciousness (Complex partial seizures)
No aura Often preceded by aura (e.g. visual
hallucinations)
Brief Last 1-2 min
Motor (focal tonic, clonic or atonic) Only motor fits
or sensory
Often there is a motor (Jacksonian)
march from face to arm to leg
No automatism Automatism may occur o automatic
DD: Tics: Unlike tics, motor semi purposeful movements of the
seizures are not under partial mouth (oral, chewing) or of the
voluntary control extremities (manipulating the sheets,
shuffling, walking).
9 Consciousness is intact. 9 Consciousness is impaired with
staring.
Postictal (Todd's) paralysis or sleepiness last minutes or hours
3. Focal seizures with secondary generalization

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4. Focal seizures epileptic syndromes:

Benign childhood epilepsy with centrotemporal spikes (BECTS)
Starts during childhood (ages 3-10 yr) and is outgrown in adolescence
The child typically wakes up at night owing to a focal (simple partial)
seizure causing buccal and throat tingling and tonic or clonic
contractions of one side of the face, with drooling and inability to
speak but with preserved consciousness and comprehension
EEG shows typical broad-based centrotemporal spikes that are
markedly increased in frequency during drowsiness and sleep
Drug of choice: Carbamazepine, oxcarbazepine
Landau-Kleffner epileptic aphasia syndrome
Focal seizures + verbal auditory agnosia and loss of speech
Drug of choice: Valproate
EEG in focal seizures
9 Shows focal spikes or sharp waves in the lobe where the seizure originates.
9 A sleep-deprived and 24-hour video EEG EEG increase diagnostic yield
B. Generalized seizures: The whole body is affected.
1. Absence seizures(Petit mal)
A. Typical Absence seizures
Incidence: More in girls. Usually start at 5-8 yr of age.
Description:
Sudden cessation of all motor activities or speech with a blank
facial expression; awareness of surroundings is cut off
Accompanied by eye lid flutter or upward rolling of the eyes
Last seconds; after seizure patient resume the pre seizure activity.
Frequently recurrent; may occur countless daily
No aura , loss of consciousness nor postictal phase
EEG o typical 3 Hz spike–and–slow-wave discharges
Hyperventilation for 3-5 min can precipitate the seizures and the
typical EEG discharges
B. Atypical absence seizures

Absences associated with myoclonic components and tone changes
of the head (head drop) and body
Precipitated by drowsiness
Usually accompanied by 1-2 Hz spike–and–slow-wave discharges

Page | 333
2. Generalized motor seizures (Grand mal)

The commonest form; pass in 3 phases.
Aura (pre ictal phase) Attack (ictal phase) Post ictal phase
A warning signs before the Sudden loss of consciousness Semiconscious for
attack may exist suggesting Tonic phase: tonic contraction of 30 min-2hr.
a focal origin of the whole body o rigid posture, apnea, Headache
epileptiform discharge: cyanosis, rolling of eyes & drolling Sleepiness
e.g. localized muscle spasm of saliva.
or paraesthesia. Clonic phase: rhythmic contraction.
& relaxation of all muscles groups o
tongue biting & loss of sphincter
control.
3. Myoclonic epilepsies
Rapid shock like contractions, usually <50 msec in duration, that may be
isolated or may repeat but usually are not rhythmic
Intact consciousness.
4. Infantile spasms
Starts in the 1st year of life
Brief symmetric tonic contractions of the neck, extremities & trunk which
may be flexor, extensor or mixed
Repetitive; usually in the morning
A cry may precede or follow the spasm; so may be confused with colic
West syndrome: triad of infantile spasms, developmental regression, and
a typical EEG ;hypsarrhythmia (high-voltage, slow, chaotic background
with multifocal spikes)
EEG o Hypsarrythmias
Normal EEG Hypsarrythmias EEG
5. Atonic or Astatic seizures

Often follow myoclonic seizures
Cause a very momentary loss of tone with a sudden fall

Page | 334
Investigation
For the first unprovoked no febrile seizure
1. EEG (Electro Encephalogram); in awake and sleep state
2. Metabolic screen: Serum Na, Ca, Mg, glucose ± inborn errors of metabolism
3. CSF examination in suspected CNS infections.
4. MRI (preferable) / CT brain for:
Patients with focal seizures
Increased intra cranial pressure
Resistance to treatment
5. ECG to rule out long QT or other cardiac dysrhythmias
6. Genetic diagnosis is now available for a huge number of seizures disorder
Treatment of epilepsy
When to start anti-epileptic drugs (AEDs)?
Low risk of recurrence High risk of recurrence

Isolated first seizure with: Seizure with:
Normal neurodevelopmental status Abnormal neurodevelopmental status
Normal EEG Abnormal EEG
Normal MRI Abnormal MRI
Absent family history of epilepsy Positive family history of epilepsy
9 No long term AEDs 9 Rule out Symptomatic Seizures

9 Close observation 9 Start AEDs even if the first seizure
9 Prescribe rescue medications (rectal
diazepam) for seizures > 5 min
For symptomatic seizures:
Treat the underlying cause (hypoglycemia, urea cycle abnormality,

meningitis, temporal lobe tumor, etc.)
Educating the family and the child about
R The disease, and its management
R How to handle seizures acutely and use of rescue medications
R Watch the child during swimming in pools, passing traffic, ….
R Never to stop the AEDs suddenly
R Exercise: can share in hockey, baseball, basketball, and football

Page | 335
Anti-epileptic drugs (AEDs)

How to start?
Choice should be based on the type of seizure and the epilepsy
syndrome
Only one drug is used with small dose o if no response o gradually
increase the dose.
Control with 1 drug (monotherapy) should be the goal
In resistant cases a 2nd drug can be used alone or in combination.
When to stop?
Children are free of seizures for at least 2 yr with normal EEG at
discontinuation
AED therapy should be discontinued gradually, over a period of 3-6 mo
Disorder Drug of first choice
Focal
Secondary generalized Oxcarbazepine, levetiracetam, carbamazepine
seizures
Absence seizures Ethosuximide (Zarontin )
Treatment is guided by EEG
Both absence & generalized
motor seizures coexist Valproate /Lamotrigine
Generalized epilepsies
Myoclonic epilepsy Valproate/ Lamotrigine
Infantile spasms Adrenocorticotropic hormone (ACTH)
Suppresses the expression of corticotrophin-
releasing hormone, a proconvulsant
neuropeptide whose expression may be
enhanced in patients with infantile spasms
Intramuscular or Gel in a tapering doses
Monitor the patient's response with serial
EEG
Vigabatrin (Sabril) ; retinal toxicity is a risk
Migraine and epilepsy Valproate or Topiramate (effective in both)
Other new FDA approved anti-epileptic medications e.g.
Perampanel (Fycompa)
Rufinamide (Banzel)
Clobazam (Onfi)

Page | 336
Na valproate Carbamazepine Levetiracetam Lamotrigine

Dose 20-40 mg/kg/d 10-20 mg/kg/d 20-40 mg/kg/d 1-15 mg/kg/d
Side Sedation Sedation Somnolence Dizziness
effect Hepatotoxic Hepatotoxic Asthenia Headache, ataxia
Alopecia Anemia Behavioral Stevens-Johnson
Weight gain Leucopenia disorders syndrome
Ketogenic diet:
For infants < 2year with resistant myoclonic epilepsy
Most calories given form fat (never used with valproate)
Differential diagnosis: from conditions mimic epilepsy
1. Vagal syncope
Triggered by sight of blood, pain, or sudden stress
There is initially pallor and sweating followed by blurring of vision,
dizziness, nausea, and then gradual collapse with loss of consciousness
Rapid recovery with no postictal depression
If prolonged ; lead to generalized convulsions, termed anoxic seizures
2. Cardiac syncope:
Long QT syndromes
Aortic stenosis
Syncope mostly predisposed by Exercise
3. Breath holding attacks
Episode starts with a cry (often a “silent” cry and marked pallor in the
case of the pallid type), and progresses to apnea and cyanosis.
Spells usually begin between 6 and 18 mo of age.
Syncope, tonic posturing, and even reflex anoxic seizures
Association iron deficiency anemia is common
4. Psychogenic nonepileptic seizures
Predisposed by stress
Gradual onset
Asynchronous flailing limb movements that vary between attacks
No injury, closed eyelids
May respond to suggestion during “loss of consciousness”
Usually >2-3 min

Page | 337
Status Epilepticus
Definition
Continuous seizure activity or recurrent seizure activity without regaining of
consciousness lasting for >30 min
Impending status epilepticus: seizures lasting between 5 and 30 min
Etiology
1. Prolonged febrile seizures (the commonest cause)
2. Sudden withdrawal of anticonvulsants in an epileptic patient
3. CNS anomalies or infections (e.g. encephalitis) or tumors.
4. Metabolic disorders e.g. hypoglycemia, inborn errors of metabolism
Clinical types
Convulsive status epilepticus (generalized tonic, clonic, or tonic-clonic)
Nonconvulsive status (complex partial, absence)
Myoclonic status
Management
A. Initial assessment
A brief physical examination should assess respiratory and circulatory
status.
A rapid neurologic examination provides a preliminary classification of the
type of status epilepticus.
A history from a parent or caregiver for possible cause of the seizures.
B. Initial intervention:
In the first 5 minutes of seizure activity
a) Airway Maintain airway.
Suction of secretions
b) Breathing O2 inhalation
Assisted ventilation
c) Circulation Secure an I.V. line
d) Draw Samples for Electrolytes, Glucose, Calcium and magnesium
Basic metabolic panel for inborn errors of
metabolism
Culture blood and CSF
Toxic screen
AEDs level in known epileptics
e) Continuous EEG Helps diagnosis
Monitor response to treatment
f) Glucose 10% 5ml/Kg For hypoglycemia

Page | 338
C. Control convulsions
Emergent therapy (6-15 minutes)
IV line available I.V slow Lorazepam (0.05mg/kg )
May be repeat in 5-10 minutes
or
Diazepam (0.3mg/kg)
May be repeat in 5-10 minutes
or
Midazolam (0.2 mg/kg )
Followed by IV infusion
(With all benzodiazepines ; monitor and manage
respiratory depression)
IV line un available Buccal or intranasal midazolam
or
Intranasal lorazepam
or
Rectal diazepam are effective options
Urgent therapy (16-35 minutes)
x Give immediately Phosphenytion or phenytion
Loading 15-20 mg/kg under ECG monitor
Not > 0.5-1 mg/kg/min
Take peak blood level 2 hr later
Maintain on 3-6 mg/kg/24 hr
x Phenobarbitone is often the next medication at a loading dose of 5-
10 mg/kg
x IV Valproate (25mg/kg) is emerging as a strong evidence urgent therapy
If seizures controlled Refractory status epilepticus

Use maintenance doses of phenytion Intubate and assist respiration
and /or phenobarbitone Drug options:
Midazolam infusion
Propfol infusion
Barbiturate coma
General anesthesia
Careful attention to blood pressure
Monitor response with EEG

Page | 339
Hydrocephalus
Definition
Excessive accumulation of CSF with enlargement of cerebral ventricles with
or without increase of the intra cranial pressure; ICP
Hydrocephalus is not a specific disease; it represents a diverse group of
conditions that result mainly from impaired circulation and/or absorption of
CSF .
Normal CSF circulation:
CSF amount in infant = 50 ml (150 in adult)
1. CSF is formed by active secretion by choroids plexus mainly in the lateral

ventricles
2. CSF passes via foramen of Monro to the 3rd ventricle
4. Then via aqueduct of Sylvius to the 4th ventricle
5. Then via foramena of Lnuscka & Magendi to the subarachnoid space
7. CSF in subarachnoid space is absorbed by arachnoid villi to dural venous
sinuses

Page | 340
Causes of hydrocephalus
I. Relative hydrocephalus: Normotensive hydrocephalus
- Apparent increase in CSF due to brain atrophy
- Not associated with raised ICP
II. Absolute hydrocephalus
A. Obstructive hydrocephalus
Obstructed CSF flow within the ventricular system (Non-communicating)
1. Obstruction of aqueduct of Silvius:
* Congenital atresia:
- May be sex linked recessive.
- May be associated with spina bifida occulta
* Obstruction from outside by:
- Brain tumors.
- Malformation of vein of Galen (&listen for A cranial bruit).
* Obstruction from inside:
- Post hemorrhagic (especially in premature).
- Post meningitis (T.B., pneumocci, mumps)
2. Congenital atresia of:
* Foramen of Monro.
* Foramina of Luscka & Magendi: Cystic dilatation of 4th ventricle
usually with cerebellar vermis agenesis (Dandy Walker malformation)
3. Arnold Chiari malformation:

Congenital downward displacement of cerebellum, pons & medulla
4. Congenital infection especially toxoplasmosis

5. Brain tumors

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B. Non obstructive hydrocephalus (Communicating) due to either:

1. Defective CSF absorption
* Subarachnoid space adhesions: - Post hemorrhagic or post meningitic
* Leukemic infiltration.
* Dural sinus thrombosis
2. Excessive CSF secretion (Rare) due to:
- Choroid plexus papilloma
- Choriod plexus congestion as in meningitis
Clinical picture
In infant
1. Head signs
Marked; as the cranial sutures are still opened and yield under rising ICP
Accelerated rate of enlargement of the head is the most prominent

sign. (increasing head circumference on serial measurements)
Fontanels are widely opened & bulging.
Sutures are widely separated.
Dilated scalp veins.
Eyes deviated downwards o Sunset appearance
Skull percussion o Cracked pot sound (Macewen sign).
Craniotabes in all bones
A foreshortened occiput suggests Chiari malformation, and a
prominent occiput suggests the Dandy-Walker malformation.
2. Neurologic sings
Mild, as rapid n in skull size protect against marked increase of ICP
Mild vomiting
Squint
Delayed motor milestones
Pyramidal tract lesion signs are common especially in lower limbs.
In advanced cases: mental retardation & optic atrophy may occur.

Page | 342
In older child
Marked neurologic manifestations as the sutures are not easily separated
with subsequent marked increase ICP
-Bursting headache; severe in the morning
-Blur of vision
-Projectile vomiting (unrelated to meals, not preceded by nausea)
-Bradycardia & hypertension (Cushing response)
Diagnosis
A. Confirm hydrocephalus
1. Clinical picture: Progressive head enlargement on serial measurements
2. Cranial X-ray
A. Before closure of sutures and fontanels:
- Wide fontanels, wide separation of sutures.

- Craniofacial disproportion with large cranium.
B. After closure of sutures and fontanels:
- Increased ICP (beaten silver appearance, wide sella)

3. Trans fontanel cranial ultrasound
4. CT & MRI
Diagnostic; can detect ventricular dilatation.
Detect degree of cortical atrophy.
May detect the cause

Page | 343
B. Type of hydrocephalus; obstructive or communicating?

1. CT & MRI: The most accurate and non-invasive ¥¥
2. Simultaneous lumbar & ventricular manometry:
- Normally, both are equal
- Ventricular pressure > spinal pressure in obstructive hydrocephalus
3. CSF examination: xanthochromia & cytoalbuminous dissociation in obstructive
type
N.B: Examination of fundus is mandatory for:
Evidence of chorioretinitis in congenital infections e.g. toxoplasmosis
Check for papilledema in older child
Treatment
Medical
Decrease CSF by:
Carbonic anhydrase inhibitors; acetazolamide (Diamox tablets)
Furosemide
For:
Moderate or slowly progressive ventricular dilatation
If response is not stable o proceed to shunt operation
Draw backs:
Transient effect
Electrolyte & pH disturbances
Surgical
1. Choroid plexectomy or diathermy for choroid papilloma
2. Extra cranial shunt operation
Types
Ventriculoperitoneal
Ventriculo artial (right)
Ventriculopleural
Complications
Shunt nephritis (immune complex mediated)
Obstruction (headache, papilledema, emesis,
mental status changes)
Infection commonly with staph epidermidis
(fever, headache, meningismus)
Relative shortening as the child grow

Page | 344
Differential diagnosis macrocephaly

From causes of macrocephaly (H.C> 2 standard deviation above mean)
Cranial causes
Constitutional
Achondroplasia
Familial
Anemia (chronic hemolytic)
Rickets
Intracranial causes
Hydrocephalus
Hydrancephaly
Space occupying lesion e.g. tumor
Megalencephaly which may be due to:
Cretinism
Storage diseases (e.g. mucopolysacharidosis).
Familial

Page | 345
Microcephaly
Definition: Head circumference measures > 3 SD below the mean for age and sex
Causes
1- True microcephaly due to small sized brain.
2- Craniosynostosis due to early fusion of sutures.
i. True microcephaly
Criteria
- Skull sutures & fontanelles o normal.
- No increase intra cranial tension.
- Skull X ray show small vault.
- CT scan shows brain atrophy.
Etiology
a. Genetic
- Familial o AR, (severe atrophy of frontal lobes o camel head)
- Chromosomal syndromes e.g. trisomy 21, 18, 13
b. Secondary (Non genetic)
* Prenatal:
- TORCH infection.
- Fetal irradiation; especially in the 2nd trimester.
- Maternal diabetes or phenyle ketonuria.
- Maternal drugs e.g. phenytoin, &alcohol.
* Natal: Hypoxic ischemic encephalopathy.
* Post-natal: Early meningitis& Encephalitis
ii. Craniosynostosis
Definition: early fusion of skull sutures;
1. Palpable ridge is felt at the affected suture.
2. If multiple sutures are affected:
- Microcephaly o brain atrophy.
- Increase intra cranial tension o hydrocephalus& beaten sliver
appearance in skull X ray.
3. Skull examination o abnormal skull shape which may be:
a. Scaphocephaly (Dolicocephaly)
Elongated due to premature closure of sagittal suture

Page | 346
b. Brachycephaly
Short anteroposterior
Due to bilateral closure of coronal sutures
c. Oxycephaly
Conical head
Due to multiple sutures closure
d. Trigonocephaly
Triangular
Due to closure of metopic suture
Treatment
Surgical separation of skull sutures is indicated in:
- Cases with hydrocephalus.
- Cases with progressively increase intra cranial tension.
- Cosmotic reasons.

Page | 347
Cerebral Palsy
(Little’s Disease)
Definition
A group of permanent disorders of movement and posture causing activity
limitation
Resulting from non-progressive lesions to the developing fetal or infant brain
Affecting mainly the motor centers; cerebral cortex , cerebellum , and basal
ganglia
With frequent neurologic associations including:
Mental retardation
Epilepsy
Impaired hearing ;deafness
Impaired vision
Emotional disturbances
Behavioral disturbances
Causes
Pre-natal (80%)
Antenatal Infections
Congenital malformations
Fetal asphyxia
Natal (10%)
Birth asphyxia
Birth trauma
Post-natal (10%)
VLBW with intracranial hemorrhage
Meningitis, encephalitis
Metabolic e.g. phenyle ketonuria
Hypoglycemia
Hyper bilirubinemia
Hydrocephalus.
Topographic classification: (distribution of motor defect)
1- Monoplegia o Only one limb is affected
2- Hemiplegia o Upper and lower limbs on one side are affected
3- Diplegia o All limbs are affected, the lower more affected than the
upper limbs
4- Paraplagia o Only both lower limbs are affected
5- Quadriplegia o All the four limbs are affected

Page | 348
Clinical Types
1. Spastic cerebral palsy
Criteria
The commonest type
Pyramidal tract lesion (UMNL) signs:
Hypertonia
Hyper reflexia
Positive Babinski sign
May be clonus
Persistence of primitive reflexes
Pesudobulbar palsy o feeding disorder (poor suckling & swallowing),
squint and speech disorders.
Types
1. Spastic diplegia: 35%
Bilateral spasticity of the legs that is greater than in the arms
More in premature with periventricular leucomalacia
Crawling is commando like rather than four limbed crawling.
Lower limbs scissoring (application of a diaper is difficult)
With paraspinal muscle involvement, the child may be unable to sit.
MRI typically shows scarring and shrinkage in the periventricular
white matter with compensatory enlargement of the cerebral
ventricles
2. Spastic hemiplegia: 25%
Due to in utero or neonatal stroke
Decreased spontaneous movements on the affected side
Shows hand preference at a very early age
Walking is delayed until 18-24 mo (tiptoe walking); gait is
circumdactive
Examination of the extremities may show growth arrest,
particularly in the hand and thumbnail
Upper extremity assumes a flexed posture when the child runs
3. Spastic quadriplegia: 20%
More ischemia and infection
The most severe type
Marked motor impairment of all extremities and the high association
with mental retardation and seizures
4. Spastic monoplegia
5. Spastic paraplegia

Page | 349
2. Ataxic cerebral palsy

Criteria
Hypotonia and hyporeflexia
Cerebellar ataxiao incoordination of voluntary movements, nystagmus,
staccato speech, intention tremors.
3. Extrapyramidal (dyskinetic, asthetoid) cerebral palsy
Commonest causes
Asphyxia, kernictrus
Criteria
Hypotonia (replaced with time with hypertonia & rigidity)
Chorio asthetoid movements.
Deafness.
3. Atonic cerebral palsy
Profound hypotonia o floppy infant
Preserved deep tendon reflexes
5. Mixed cerebral palsy
Diagnosis
1. Clinical: A thorough history and physical examination should rule out a
progressive disorder of the CNS, including degenerative diseases,
metabolic disorders, spinal cord tumor, or muscular dystrophy
2. Investigations:
Value: Exclude progressive brain insults and may detect a cause or association
a. CT & MRI
May detect the cause e.g. brain malformations and spinal cord lesions
Rule out brain tumors & degenerative brain disease.
CT scan may be useful for detecting calcifications associated with
congenital infections
b. TORCH screen.
c. Genetic evaluation
d. Metabolic screen.
e. For associations: Test for Hearing, Visual function , EEG for seizures
N.B Conditions that can mimic cerebral palsy

• Spinal cord tumors
• Channelopathies
• Sandifer syndrome
• MECP2 duplication
• Congenital dopa-responsive disorders
• Genetic spastic paraplegia
• Some metabolic conditions (GLUT1 deficiency, glutaric aciduria type 1)
• Ataxia telangiectasia

Page | 350
Treatment
Multidisciplinary approach is most helpful in the assessment and treatment
of such children; A team of physicians from various specialties as:
Occupational and physical therapists
Speech pathologists
Social workers
Educators
Developmental psychologists
Assist:
Feeding & defecation
Vision and hearing
Walking: Walkers, standing frames, motorized wheel chair
Communication by talking typewriters and special computers
Rehabilitation according to the degree of motor disability
Medications
Anti spastic drugs
drug Action Side effect
Diazepam GABA agonist Sedation
Useful in short term relief of painful Dependency with long
spasms term use
Baclofen GABA agonist and inhibit spinal Sedation
neuronal transmission
When used intrathecally, via a surgically
implanted continuous-GHOLYHU\SXPSĺ
greater efficacy with fewer adverse
effects
Tizanidine Alpha-2 adrenergic receptor agonist and Sedation
inhibit spinal neuronal transmission
Useful in severely disabled by cerebral
palsy and in those with night-time
spasms
Dantrolene Block calcium intake by skeletal Hepatic dysfunction
musclesĺ Ļ free intracellular calcium Blood dyscrasia
Botox A: injection in spastic muscles and salivary glands to reduce
drooling. It stops the release of acetylcholine at the synapse and blocks
neurotransmission. The effects gradually wear off (over about 3–6 months)
Levodopa: Small doses may be helpful for dystonia and rigidity
Surgery:
For marked spasticity of the lower H[WUHPLWLHVĺsurgical soft tissue
procedures that reduce muscle spasm e.g. adductor tenotomy or psoas
transfer and rhizotomy (roots of the spinal nerves are divided)

Page | 351
Mental Retardation
Definition: Handicapping disorder with age of onset below 18 years characterized
By subnormal I.Q. (< 70%).
Mental age
I.Q. (Intelligence Quotient) = u100
Chronological age
Diagnostic criteria
1- Subnormal intelligence quotient “IQ” (less than or equal to 70%)
2- Limitations exist in two or more of the adaptive skills e.g.
communications, social skills, self care, safety, functional academics, work
3- Manifest before age of 18 years (if after 18 years, it is called dementia.)
Etiology
1.Physiologic (sub cultural)
x No demonstrable organic brain lesions
x Seen in children living in low socio economic standard with neglect
and poverty
2.Genetic causes
x Chromosomal anomalies; e.g. Trisomy 21,18,13, klinefelter syndrome
x Genetic disorders e.g. Fragile-X syndrome , prader willi syndrome
x Developmental brain abnormalities e.g. hydrocephalus and familial
microcephaly
x Degenerative brain diseases e.g. lipidosis and mucoploysacridosis
x Inborn errors of metabolism
2.Non genetic
x Cerebral palsy causes (Mention)
x Congenital hypothyroidism
x Severe hypernatremia or recurrent hypoglycemia
Presentations
Age Manifestation
Infancy Delayed social development oFail to interact with
environment
Gross motor delay
Early Language delay /difficulties
childhood Behavior difficulties
Delayed fine motor
Late childhood Academic under achievement
Prevention
Proper prenatal, natal and post-natal care
Vaccination against rubella for females (not during pregnancy)

Page | 352
Neonatal screening to identify preventable causes of MR (e.g.

phenylketonuria).
Treatment of neonatal jaundice, hypoglycemia, hypothyroidism ….
Evaluation:
1. Neuro imaging o CT , MRI
2. T4 ,TSH
3. Karyotyping
4. Fragile X screen
5. Metabolic o e.g. plasma amino acids , urine organic acids , …
Treatment
Only rehabilitation of the child depending on the degree of mental retardation:
Mild (IQ 50-70) o educable (may need special classes)
Moderate (IQ 35-50) o trainable (they are trained to care for themselves)
Severe (IQ 20-35) o r trainable.
Profound (IQ 0-20) o non trainable (so, they need full time nursing care).

Page | 353
Acute post infectious polyneuropathy

(Gillian Barre syndrome)
Etiology
Auto immune, often postinfectious polyneuropathy involving mainly motor
but also sensory and sometimes autonomic nerves
Paralysis usually follows a nonspecific gastrointestinal (especially
Campylobacter jejuni, or Helicobacter pylori) or respiratory infection
(especially Mycoplasma pneumonia) or viral infections.
Clinical picture
1. Motor : Acute ascending flaccid paralysis:
Criteria:
Bilateral & symmetric usually (asymmetric in 9%)
Associated hyptonia & hyporeflexia.
Progress:
Lower Limb (inability or refusal to walk)o trunk o upper limb.
Bulbar palsy (in 50%) o dysphonia, dysphagia & lost bulbar reflexes.
Respiratory muscles o respiratory failure.
9 Miller-Fisher syndrome consists of acute external ophthalmoplegia,
ataxia, and areflexia
2. Sensory
Mild
Tender calf
3. Autonomic
Labile blood pressure & heart rate
Urinary incontinence or retention of urine in about 20%
Diagnosis
9 CSF: Cyto albuminous dissociation :
High CSF protein > twice the upper limit of normal and a lack of
cellular response < 10 white blood cells/mm3
Negative bacterial culture
9 MRI of the spinal cord
Thickening of the cauda equina and intrathecal nerve roots in >90% of
patients
Rule out other spinal disorders
Motor nerve conduction velocity are greatly reduced
Electromyography shows evidence of acute denervation of muscle.
Serum creatine kinase (CK) level may be mildly elevated or normal

Page | 354
Treatment
Patients in early stages of this acute disease should be admitted to the
hospital for observation because the ascending paralysis can rapidly
involve respiratory muscles during the next 24 hr
i. Supportive:
Respiratory effort monitoring (spirometry) and support
Cardiac monitoring
Nasogastric feeding
Care of bladder (catheterization & neostigmine).
Physiotherapy
ii. Specific
IVIG: A commonly recommended protocol is IVIG 0.4 g/kg/day
for 5 consecutive days, but some studies suggest that larger doses
are more effective (1 g/kg/day for 2 consecutive days)
Alternatives: if IVIG is ineffective
Plasmapharesis is equally effective as IVIG.
Combined IVIG and interferon is effective in some patients
Steroids are not effective
Differential diagnosis: Other causes of acute flaccid paralysis
Prognosis
x The clinical course is usually benign, and spontaneous recovery begins
within 2-3 wk.
x Most patients regain full muscular strength, although some are left with
residual weakness.
x Improvement usually follows a gradient opposite the direction of
involvement: bulbar function recovering first, and lower extremity
weakness resolving last.
Differential diagnosis : Acute Flaccid Paralysis
A. Acute asymmetrical paralysis
- Cerebrovascular stroke e.g. acute hemiplegia
- Poliomyelitis
- Pseudo paralysis e.g. with osteomyelitis, trauma, scurvy
B. Acute symmetrical paralysis
* Spinal cord: Trauma, Compression by abscess or tumors, Transverse myelitis
* Infections: Botulism, Diphtheria, Rabies
* Post infections: Gillian Barre syndrome, Enterovirus Associated Post Infectious
Myelitis (Recently discovered in USA)
* Tick-bite paralysis
* Myasthenia gravis
* Hypokalemic periodic paralysis

Page | 355
Inability To Walk
Normal walking require integration between CNS, muscles, skeleton and training
Causes of delayed walking
A. Central causes:
1-Brain - Cerebral palsy
- Mental retardation
- Hydrocephalus
- Congenital malformations
- Brain damage with tumors or infections
2- Spinal cord - Congenitalo Spina bifida.
- Traumatico Spinal cord trauma.
- Inflammatoryo Pott’s disease of the spine.
- Neoplastico Spinal cord tumors.
3- Anterior horn cells - Poliomyelitis.
- Spinal muscle atrophy.(Werding Hoffman disease)
4- Peripheral Nerve - Guillian - Barre syndrome..
- Polyneuritis (Diphtheria, Drugs)
5- Neuro muscular junction - Mysthenia gravis.
- Botulism
- Organophosphorus poisoning.
B. Muscular causes:
* Primary muscle disorders: Myopathies, Myositis and Metabolic.
* Secondary muscle disorders: Rickets and malnutrition.
C. Skeletal: (Bones, Joints)
- Rickets
- Inflammation (arthritis, osteomyelitis)
- Lower limb trauma
Differential diagnosis of inability to walk:
Causes Primary Secondary
( The child has not walked before) ( The child has walked before)
a.Paralytic - Early poliomyelitis. - Poliomyelitis.
- Early paralysis before walking. - Post diphtheric paralysis
- Cerebral palsy - Post encephalitic paralysis
- Cerebro-vascular accidents
b.Non paralytic - Rickets - Rickets.
- Mental retardation - Malnutrition.
- Simple delayed walking - Fractures or osteomyelitis

‫‪Notes‬‬

‫‪Notes‬‬

‫‪Notes‬‬

‫‪Notes‬‬


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

Dr Osama Taha Amer

And finally I end my foreword with these lines to Richard Templer:

Richard Templer (The rules of life)

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‪.‬‬

Lt. V. : Left ventricle

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Diagnosis of a cardiac patient

o Systemic venous p Low cardiac output

Suspected congenital heart disease Suspected rheumatic heart disease

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Remember the following notes

* Left atrium does not appear

* Any chamber enlarges in

* Ventricles depolarize from

* After birth pressures in the

* Pressure values increase

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Step 3 : Precordial examination

Right - Apex beat is shifted directly out

Tall ,peaked P wave (P-pulmonale)

wide and bifid P wave (P-mitrale)

Evidence of pulmonary artery dilatation in cases with pulmonary hypertension(PH)

Pan systolic Ejection systolic Early diastolic Mid diastolic

Congenital Heart Diseases (CHD)

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Acyanotic Congenital Heart Diseases (ACHD)

ACHD constitutes 80% of all CHD

3. Heart failure 4. Eisenmenger syndrome: Prolonged high

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Outlet defect; (also called

x Blood is shunted from the left ventricle(higher

x Increased pulmonary blood flow

x Pulmonary congestive symptoms

Small VSD Large VSD

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Small VSD Large VSD

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Atrial Septal Defect (ASD)

Definition: Defect in the inter-atrial septum.

Secundum ASD Primum ASD

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Apex Lower left sternal border

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

(Chest x ray after ASD device closure, source: Radiopaedia.com)

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Patent ductus arteriosus (PDA)

1. Small duct 2. Big duct

R Asymptomatic ; discovered R Symptoms of increased

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Differential diagnosis of continuous murmurs:

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Atrio ventricular septal defect (AVSD)

Clinical picture is very similar to large VSD and

.‫ﺟﻌﻠﻪ ﺍﻟﻠﻪ ﺻﺪﻗﺔ ﺟﺎﺭﻳﺔ ﻟﻲ ﻭﻟﻮﺍﻟﺪﻱ ﻭﻟﺬﺭﻳﺘﻲ‬

Coarctation of Aorta (CoA)

Constriction of the aorta to anywhere from aortic arch to aortic bifurcation.

1. Hypertension proximal to the

x Pulmonary congestive symptoms

Spell lasts from a few minutes to a few hours

ECG o Right bundle branch block (RBBB) and RAD

Positive throat culture Or