مذكرة فرست الزمالة المجمعة

Basics for Egyptian Fellowship of Pediatrics (step 1) CVS
Cardiovascular System
Prepared by Dr. .. 1 Typed by M.A

Embryology & congenital anomalies

- The heart is developed during the period of embryogenesis from a primitive
single endocardial tube.
- The endocardial tube grows and fills the pericardial cavity. It will form the
endocardium of the heart.
- The splanchinic mesoderm surrounding the heart tube is differentiated into the
myocardium and the pericardium of the heart.
- Two constrictions appear in the heart tube dividing it into 3 chambers: atrium,
ventricle and bulbus. The bulbus is continuous with the aorta.
- Later on, the sinus venosus appears as a constricted portion from the atrium,
and it receives all the body veins.
Now, the heart tube consists of four chambers:
1. Sinus venosus. 2. Atrium.
3. Ventricles. 4. Bulbus.
- A fifth dilatation is formed next to the bulbus,
known as the truncus arteriosus.
∙ Internal changes in the heart tube:
- The sinus venosus consists of right and left horns,
each of them receives:
1. Common cardinal vein from the body of the
embryo.
2. Vitelline vein from the yolk sac.
3. Umbilical vein from the placenta.
- The right horn is absorbed into the wall of the right atrium and forms its
posterior smooth portion.
- The left horn is atrophied and forms the coronary sinus and the oblique vein of
left atrium.
- The right common cardinal vein forms the lower half of the S.V cava.
- The right vitelline vein forms the proximal portion of the I.V cava.
- The right umbilical vein is obliterated later on.
➢ Development of the atria:
- The single atrium communicates with the ventricle by a narrow canal called the
atrio-ventricular canal. Then, the septum intermedium develops and divides the
canal into right and left canals.
∙ The septum primum:
- It is a downward growth from the wall of the single atrium dividing it into two
chambers right and left.
- The lower end of the septum primum leaves an opening, the ostium primum,
which communicates right and left atria. Later on, it is closed.
- Before the septum primum is completely closed, series of perforations appear
near its cranial end, the ostium secondum (foramen ovale)
∙ The septum secondum:
- It develops just to the right and parallel to the septum primum, it grows
downwards to cover the ostium secondum.
- After birth, the pressure in the two atria is equal and the two septa fuse with
each other.
➢ Development of the ventricles:

- The primitive ventricle and the proximal part of the bulbus cordis share in the
formation of the ventricles.
- A muscular interventricular septum grows and separates it into left and right
ventricles.
- The interventricular foramen is closed by a membranous interventricular
septum.
➢ The truncus arteriosus:

- A pair of opposing ridges appear in the truncus arteriosus.
- They enlarges and fuse to form the truncus septum, which divides the truncus
arteriosus into the ascending aorta and the pulmonary trunk.
➢ Aortic arches:
- There are 2 ventral and 2 dorsal aortae.
- The 2 ventral aortae unite to form the aortic sac.
- The 2 dorsal aortae lie behind the gut
- From the ventral aortic sac, 6 aortic arches radiate around the pharynx to
reach the dorsal aortae.
∙ Fate of the aortic arches:
- 1st and 5th : disappear.
- 2nd : disappears except a small part forming the stapedial artery.
- 3rd: common carotid and proximal part of the internal carotid arteries.
th
- 4 : Rt side: subclavian artery Lt side: forms part of the aortic arch.
th
- 6 : Rt side: ventral part: rt pulmonary a. dorsal part: disappears.
Lt side: ventral part: lt pulmonary a. dorsal part: ductus arteriosus.
Fetal Circulation
- Oxygenated blood comes from the Placenta, which acts as a lung for
oxygenation of the fetal blood.
- The oxygenated blood reaches the fetus from the placenta via the left umbilical
vein.
- The left umbilical vein reaches the liver of the fetus.
- In the liver, most of the oxygenated blood passes through the ductus venosus to
reach the I.V.C. And a little amount of blood passes through the liver sinusoid,
then to the I.V.C.
- The I.V.C (mixed blood): carries oxygenated blood from the left umbilical vein
(from the placenta) mixed with a little amount of deoxygenated blood from the
lower half of the fetus. The I.V.C finally opens in the right atrium.
- In the right atrium most of blood of the I.V.C is directed through the foramen
ovale to the left atrium and aorta, where it is distributed mainly to the heart,
head and neck and upper limbs.
- The deoxygenated blood carried by the S.V.C reaches the right atrium. It
passes directly to the right ventricle, and then to the pulmonary trunk, where a
little amount goes to the lungs (collapsed) and the majority of blood escapes
through the ductus arteriosus to the distal part of the arch of aorta to be mixed
with the oxygenated blood.
- The dorsal aorta carries partially oxygenated blood, distributed to abdomen
and lower limbs, and finally passes through the two umbilical arteries to the
placenta to be oxygenated and returned to the embryo again via the umbilical
veins.

∙ Changes in the fetal circulation after birth (circulatory adaptation after birth):
birth)
A) Immediate changes:
1) Establishment of the pulmonary circulation: stoppage of the placental blood
flow results in anoxia, which stimulates the pulmonary center of the fetus leading
to lung expansion, negative intrathoracic pressure and suction of the blood into
lungs and establishment of the pulmonary circulation.
2) Functional closure of the foramen ovale: establishment of the pulmonary
circulation increases the pressure in the left atrium, while the stoppage of the
placental blood flow decreases the pressure in the right atrium. These two
changes cause firm opposition of the septum primum to the septum secondum
and closure of the foramen ovale.
3) Functional closure of the ductus arteriosus: immediately after birth by
contraction of its thick muscular wall resulting in:
a. cutting the shunt between the left pulmonary artery and the aortic arch.
b. passage of all blood from the pulmonary trunk to lungs.
B) Late fibrotic changes:
- During the first year of postnatal life, some of vessels become fibrosed and
change into ligaments, as follows:
1) Left umbilical vein..... ligamentum teres of the liver.
2) Ductus venosus..... ligamentum venosum of the liver.
3) Ductus arteriosus..... ligamentum arteriosum connecting the left pulmonary
artery to the arch of aorta.
4) The umbilical arteries..... lateral umbilical ligaments.
Congenital Anomalies of the heart

1. Atrial septal defects: - persistent foramen ovale.
- persistent ostium primum.
2. Interventricular septal defect:
- Patent interventricular foramen.
- Agenesis of the interventricular septum.
3. Agenesis of the truncus septum:
- Persistent truncus arteriosus.
4. Fallot's tetralogy: pulmonary stenosis, hypertrophy of the right ventricle,
patent interventricular foramen, over-riding of aorta.
5. Anomalies of the valves:
- Atresia or stenosis.
- Extra-cusp or reduced cusp.
6. Anomalies of the heart position:
- Dextrocardia, isolated or situs inversus totalis.
- Ectopia cordis (the heart is exposed in the chest)
- High position due to failure of descent.
7. Anomalies of Aorta:
- Coarctation of aorta.
- Rt and double aortic arch.
- Missed coronary artery.

Physiology
Central Venous Pressure (CVP)
- Normal CVP is 2-12 cm H2O, varies with cardiac cycle, respiration and
position of the person.
∙ Causes of decreased CVP: non cardiogenic shock.
∙ Causes of increased CVP: - heart failure.
- positive end expiratory pressure ventilation, and
Valsalva's maneuver which impedes the venous
return.
- expansion of the blood volume.
Cardiac Output
CO = HR X SV = 72 X 70 / 1000 = 5 L / min. in average resting man.
∙ The cardiac index:
it is the CO per square meter of body surface = 3.2 L
∙ Measurements of CO:
Fick method, Dye method, Thermodilution
- Fick method:
the amount of oxygen delivered to tissues must equal the oxygen uptake by lungs
plus oxygen delivered to lungs in the pulmonary artery.
- Dye method: …
- Thermoregulation:
a cold saline is injected at the proximal end of a catheter in the right ventricle.
∙ Factors modifying CO: HR & SV

- HR: intrinsic rhythmicity & extrinsic factors e.g: autonomic N.S.
- Stroke volume: contractility, preload(venous pressure), afterload (arterial B.P)
∙ Contractility:
- Causes of increased contractility: (positive inotropic factors)
1. sympathetic nerve stimulation and catecholamines.
2. increase in the extracellular Calcium.
3. decrease in the intracellular Sodium.
4. Drugs e.g: digoxin, L-thyroxin.
- Causes of decreased contractility: (negative inotropic factors)
1. Drugs: β-blockers, antiarrhythmic drugs, anesthetic drugs.
2. Heart failure.
3. Hypoxia, hypercapnia, acidosis.
∙ Preload: CVP = Lt ventricular end diastolic volume

- determined by: blood volume, venous tone and gravity and respiratory and
muscle pumps.
∙ Afterload: A.B.P
- determined by: CO and total peripheral resistance (aortic valve resistance,
aortic pressure, ventricular cavity size).
Arterial Blood Pressure

- Blood pressure = CO X PR (peripheral resistance)
- Pulse pressure = systolic – diastolic pressure.
- Main arterial pressure = diastolic – ⅓ of the pulse pressure.
∙ Controls: - Renin-angiotensin system.
- Autonomic N.S via baroreceptors in aortic arch via vagus and
carotid sinus and medullary and hypothalmic cardiorespiratory centers .
∙ Main determinants of the blood pressure:
1. H.R: increase in the heart rate leads to increase in the arterial B.P.
2. P.R (peripheral resistance) = mean ABP / CO = 100 / 5 = 20 mmHg.
3. Stroke volume:↑ SV →↑arterial blood volume & pressure and pulse pressure.
4. Aortic elasticity: ↑ →↑ pulse pressure (↑systole, ↓diastole)
➢ Circulatory Adaptation:
1. Postural changes from supine to upright position:
↓venous return and ↓CVP → ↓Stroke volume → ↓CO → ↓B.P →
Compensatory ↑ HR & PR.
2. Severe hemorrhage:
- ↓B.P → V.C → ↓ renal blood flow
- ↑HR → ↑SV → ↑CO
3. Exercise:
- ↑HR & SV → ↑CO which is redistributed to working muscles.
- O2 consumption in blood to skeletal muscles and coronary circulation.
- Peripheral vasoconstriction increases the systemic arterial B.P.
- Pulmonary vessels dilatation → ↓ in pulmonary vascular resistance.
4. Altitude:
↓ pressure of O2 in inspired air → hypoxia → ↓ CO → ↑ H.R
5. Valsalva's maneuver:
- ↑ intrapulmonary and intrathoracic pressure → ↓ VR → ↓ H.R, SV, B.P
- On release: ↑peripheral volume → overshooting of B.P and ↓ HR.
➢ Regulation of the Arterial Blood Pressure:

Whenever arterial blood pressure is altered, the following 3 mechanisms are
brought into action respectively to restore its normal level:
I. Short term mechanisms:
- They act within few seconds, last for several hours then decline.
- They are mostly nervous reflexes that adjust the vascular capacity and
resistance, as well as CO. They include:
1. Arterial baroreflexes (pressure buffer system):
- Site: they locate in the carotid sinus and the aortic arch.
They are stretch receptors. They discharge signals, in response to increase in the
A.B.P, to buffer nerves resulting in stimulation of the vasodilator (VD) centers
and CIC, and inhibition of the vasoconstrictor centers (VCC). This decreases
A.B.P through:
a) decreasing cardiac pumping power and CO by causing bradycardia.
b) decreasing PR through vasodilatation of arterioles and venules.
c) decreasing catecholamines from adrenal medulla.
The opposite effects occur in case of decrease in the A.B.P.
This mechanism is lost in long standing cases due to adaptation.
2. Arterial chemoreceptors:
- Site: carotid and aortic bodies.
- They respond to decrease in the A.B.P (60 mmHg) due to hypoxia, and
discharge signals in the buffer nerves leading to stimulation of the VCC and
inhibition of CIC and VDC. This elevates B.P through:
a) increase cardiac pumping power and cardiac output (tachycardia)
b) increase in PR by vasoconstriction effect.
c) increase catecholamines secretion from adrenal medulla, which augments
tachycardia and vasoconstriction.
- The opposite effects occur in case of increase in A.B.P
3. The CNS ischemic response:
- Decrease in B.P below 60 mmHg, stimulates VCC leading to generalized VC
and subsequent increase in B.P which maintains cerebral blood flow.
4. The abdominal compression reflex:
stimulates the VCC → stimulation of medullary reticular formation → sends
signals in somatic nerves to skeletal muscles (mainly the abdominal) to increase
the tone → ↑ intra-abdominal pressure → compression of the abd. veins. This
increases the venous return and elevates the blood pressure.
II. Intermediate-term mechanisms: (act within minutes and last for days)
- control BP by adjusting vascular capacity and blood volume.
1. Capillary fluid shift mechanism:
- Increase in BP due to increase in the blood volume elevates the capillary
hydrostatic pressure. This leads to filtration in tissue space and decrease in
blood volume with subsequent decrease in BP.
2. Stress relation mechanism:
-The increase in BP stretches the arterioles and increases tension on their walls.
After a while, arteries relax, tension in their walls is relieved and the blood
pressure decreases.
3. Renin-angiotensin vasoconstriction mechanism:
- The decrease in BP leads to relative renal ischemia, which stimulates renin
secretion and formation of angiotensin I that is converted by angiotensin
converting enzyme to angiotensin II, a potent vasoconstrictor, increasing BP.
4. Right atrial mechanism:
- Increase in blood volume stimulates receptors in right atrium. This results in
vasodilation, release of atrial natriuretic peptide and inhibition of ADH
secretion. This increases salt and water excretion and decreases BP.
III. Long-acting mechanisms:
- These mechanisms regulate BP by adjusting body fluids and blood volume:
1. Glomerular filtration.
2. Secretion of aldosterone hormone.
Fall in BP:
- decreases glomerular filtration and urine flow, and consequently decreases salt
and water loss.
- stimulates renin and angiotensin II with their vasoconstrictor effect. This
stimulates aldosterone secretion.
- The end result is increase in blood volume and blood pressure.
Shock
➢ Definition: it is a clinical syndrome of circulatory failure (inadequate tissue
perfusion, low cardiac output and hypotension)
➢ Classification (causes, types):

I. Aetiologic classification:
1. Hypovolemic shock: (cold shock)
It occurs as a result of severe reduction in blood volume:
- dehydration - severe haemorrhage
- 3rd spacing of fluids: vasodilation, burns.
2. Cardiogenic shock:
- Heart failure, severe vascular dysfunction, ventricular arrhythmia, acute
myocarditis, extensive myocardial infarction.
3. Distributive shock: (warm shock)
as a result of wide-spread vasodilation, while blood volume is normal.
- Septic shock (gm -ve bacteria) → cytokines → vasodilation → shock.
- Anaphylactic shock: exposure to Ag → Ag-Ab reaction → histamine release
with wide-spread vasodilation and shock.
- Neurogenic shock: severe pain or fear results in failure of sympathetic
vasoconstrictor tone, generalized vasodilation and shock.
4. Obstructive shock:
It results from obstruction to blood flow in lungs or heart:
- Inflow obstruction: temponade, cardiac tumor,..
- Outflow obstruction: malignant hypertension, pulmonary embolism,..
II. According to blood pressure:
1. Compensated: normal to high blood pressure and cardiac output.
2. Decompensated: low blood pressure and cardiac output.
III. According to cardiac output:

- Normal.
- Low cardiac output: cardiac, hypovolemic.
- High cardiac output: septic, anaphylactic.
IV. According to stage:

- Reversible
- Irreversible
V. According to intravascular volume:

- Normo- or hypervolemic: cardiogenic shock.
- Hypovolemic: Loss of volume: hge, diarrhea and vomiting, burns, nephrotic.
Decreased venous return: anaphylactic, neurogenic, septic.
➢ How does shock cause death?

Severe shock may be fatal if not rapidly and properly managed.
- Death occurs as a result of development of multiple positive feedback
mechanisms, for example:
∙ Hypotension results in cerebral ischemia, which inhibits vasoconstrictor center
leading to vasodilation and bradycardia and more hypotension follows, then
death.. . Also, hypotension causes myocardial ischemia .. low CO .. more
hypotension .. death.
∙ A late cause of death is pulmonary damage due to pulmonary microembolisms
(Adult RDS).
➢ Clinical Stages of Shock:

1. Early shock: peripheral hypoperfusion, tachycardia
2. Established shock: poor peripheral perfusion, tachycardia and hypotension.
3. Advanced shock: vital organ hypoperfusion, multiple organ system failure.
4. Irreversible shock: irreversible cellular damage and refractory metabolic
acidosis.
Irreversible shock: (refractory shock)
- It is a terminal fatal stage of shock, particularly in the hypovolemic shock,
depending largely on the amount of the blood loss and how the case is managed.
- At this stage, there is no response to vasoconstrictor drugs and decrease in the
cardiac output and venous return, even if the blood volume is restored.
∙ How
Ho does irreversible shock occur:
- It occurs as a result of spasm of the precapillary sphincters and venules,
especially in the splanchinic area. This decreases capillary perfusion leading to
hypoxic tissue damage within 3-4 hrs.
- Relaxation of these precapillary sphincters while the venules are still
constricted leads to stagnation of blood in capillaries, and hypoxia continues
with more tissue damage, and the large amount of fluid escapes into tissue
spaces. At this level, shock becomes irreversible.
➢ Treatment of Shock:
I. Treatment of the cause.
II. Restoration of tissue perfusion by:
∙ General measures: for all types of shock.
- Vasopressor agents.
- Keeping patient in recumbent position.
∙ Specific measures for each type of shock:
- Hypovolemic: blood transfusion.
- Anaphylactic: adrenaline.
- Cardiogenic: dopamine.
- Septic: antibiotics, antipyretics, cortisol.
N.B: Causes of SHOCK:

Septic Hypovolemic Obstructive Cardiogenic Kinetic or distributive
Edema
A collection of excess interstitial fluid, i.e: positive interstitial fluid pressure.
∙ Causes:
1. Increased capillary hydrostatic pressure: venous obstruction, excess blood
volume, cardiac failure.
2. Decreased plasma oncotic pressure: hypoproteinemia, nephrotic syndrome,
liver cirrhosis.
3. Increased capillary permeability: allergy, bacterial disease, sepsis.
4. Increased tissue oncotic pressure: lymphatic blockage.

Normal ECG
- P wave: arterial depolarization
- QRS Complex: ventricular depolarization. Q wave is frequently absent
- T wave: ventricular repolarization.
- PR interval: ≤ 0.16 sec.
- QT interval: from the beginning of Q to the end of T.
- Heart rate: the interval between two successive QRS complexes.
Pathology
Rheumatic fever
Def.: An autoimmune disease characterized by inflammatory changes in the
fibrous tissue of different body structures, especially the heart and joints.
N.B: it is more in females from 5 to15 yrs.
1) The connective tissue of the heart:
a. Acute inflammatory stage (2-3 weeks): exudative reaction
- The myocardium shows cellular infiltrate and damage to muscle cells.
- The pericardium is covered with a fibrous exudate.
- The endocardium and the valve leaflets: edema and infiltration with a fibrous
exudate.
b. Proliferative stage:
- Myocardium: Aschoff's body (pathognomonic for rheumatic fever) consisted of
large multinucleated cells arranged around an avascular core of fibrinoid
material and may lead to fibrosis. (more in the interventricular septum and the
posterior wall of the left atrium and the left ventricle)
- Valve leaflets: vegetation (firm adherent causing no emboli) consists of masses
of eosinophilic material along the edge of the valve and may lead to fibrosis and
scarred thickened valve cusps.
2) The connective tissue of synovium and skin:
Edematous cellular infiltrate – serous effusion into the joint space.
N.B: Erosion of joint surface or pannus formation are never presents.
3) CNS:
Cellular degeneration and hyalinization of small blood vessels, scattered
through cortex, cerebellum and basal ganglia.
N.B: No Aschoff's bodies has been found in the CNS.
4) Subcutaneous nodules:
Central area of fibrinoid nectrotic material, surrounded by fibroblasts and
occasional lymphocytes.
N.B: In rheumatic endocarditis: the mitral valve is the most affected followed by the
aortic valve. Fibrin and blood cells are deposited along the borders of the valve. As the
inflammation subsides, residual scarring occurs. And with repeated attacks, scarring and
fibrosis extend to the mural endocardium and chorda tendineae.
Endocarditis
Def.: Inflammation of the valvular endocardium.
Types:
Types
I. Non-bacterial endocarditis:
1- Rheumatic endocarditis.
2- Non-bacterial thrombotic endocarditis.
3- Atypical verrucas “Libman sacks endocarditis”. (lupus endocarditis)
4- Viral, fungi. 5- Lupus?
II. Bacterial endocarditis:
1- Acute, subacute.
2- T.B, syphilis.
Another classification:
I. Infective: bacterial, viral, others..
II. Non-infective: rheumatic fever, SLE,..
Pathology of infective endocarditis
Def.: infection of the endocardial surface of the heart or the intimal surface of
certain arteries, endarteritis?, as coarcted segment of aorta and PDA.
Aetiology:(causative
Aetiology organisms)
1- Streptococcus viridans (50% of cases)
2- Staph. aureus (the next common organism and it is the most common in patients
having no underlying heart disease)
3- Enterococci (following GIT and genitourinary surgeries)
4- Pseudomonas and serratia (in I.V drug users)
5- Fungal (after open-heart surgery)
6- HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, kingella)
Pathology:
Pathology
(1) Cardiac lesions:
- The commonly affected valves are: Mitral & Aortic. However, gonococcal
infection mainly affects the tricuspid valve.
- The affected valve shows: suppurative inflammation with ulceration and
perforation of the cusps.
- Bulky septic vegetation develops on the surface of the inflammed cusps,
chordae and mural endocardium. They are friable, yellowish in color and
consists of fibrin, platelets and bacterial colonies.
- Fragmentation of vegetation leads to septic emboli resulting in pyemic
abscesses.
(2) Embolic lesions: detached vegetation forms emboli leading to:
a. Infarctions: spleen, kidney, brain,..
b. Retina: necrosis and blindness due to retinal artery embolism.
c. Coronary artery: embolism (rare).
d. Mycotic aneurysms: in cerebral and mesenteric arteries. The aneurysm
results from dilatation of the weak fibrosed part of the artery.
e. Focal embolic glomerulonephritis: small emboli causes necrosis in the
glomerular capillaries.
The surface of the kidney shows reddish spots “flea-bitten kidney”.
(3) Toxic lesions:
- Degeneration of liver and kidney and splenomegaly.
- Petechial haemorrhage in skin and mucous membrane.
Acute Infective Endocarditis Subacute Infective Endocarditis

Aetiology
- Highly virulent organisms that affect - Less virulent organisms: strept. virulans (95%)
healthy valve such: affects only rheumatic valvitis, congenital
staph. aureus, strept. hemolyticus, gonococci anomalies, prosthetic valves.
- The organism reaches the blood in severe - The organism reaches the blood in
infections (septicemia) bacteremia e.g after tooth extraction or tonsillectomy
Pathology & Complications
1. Valve Lesions
- Mitral and aortic valves are the most - Mitral and aortic.
affected, tricusped in I.V drug users - The affected valve and the mural
(pseudomonas and serratia) endocardium shows:
- The mural endocardium and the affected 1. The original pathological lesion.
valve show: 2.vegitation:
1. acute suppurative inflammation leading Gross: multiple, large, grey, friable,
to ulceration and perforation. anywhere on cusps or mural endocardium.
2. vegetation: Microscopic: consists of fibrin, bacteria
Gross: multiple, bulky, yellowish grey, and some inflammatory cells, mainly
friable, anywhere on the cusps. histiocytes.
Microscopic: consists of platelets, fibrin,
bacteria, neutrophils and pus cells.
2. Embolic Lesions
- Detachment of septic vegetation lead to - Organisms are of low virulence, so there
systemic pyemia. is no pyemia but: infarction, mycotic
aneurysms and Osler's nodules (small
tender intracutaneous nodules in bulbs of
fingers and toes.
3. Toxic Lesions
- Severe toxemia as a part of septicemia - Moderate toxemia, causing fever,
clubbing of fingers, splenomegaly, petechial
hge and focal GN (flea-bitten kidney)
Prognosis
- Rapidly fatal due to: - Can be treated, patient survives longer
1. Severe toxemia (septicemia) than acute type.
2. Cusps perforation (incompetence) - Healing by fibrosis leading to stenosis or
incompetence.
Myocarditis
Def.: inflammation of the myocardium.
Types: 1. Rheumatic myocarditis (see above)
2. Viral myocarditis.
3. Toxic myocarditis.
4. Suppurative myocarditis.
5. T.B myocarditis.
6. Syphilitic myocarditis.
∙ Viral Myocarditis:
may complicate viral diseases (adenoviruses and coxsackie virus B)
Acute:
direct tissue invasion and cellular degeneration, necrosis and infiltration with
subsequent fibrosis.
Chronic “immune-mediated” myocarditis:
- Persistence of viral RNA and DNA in the myocyte resulting in viral-host
antigenic alterations.
- This stimulates the host immune response (Cytotoxic lymphocytes and natural killer
cells) leading to autoimmune damage of myocytes and dilated cardiomyopathy.
∙ Toxic Myocarditis:
- caused by severe bacterial toxemia (e.g: diphtheria, pneumonia, typhoid) or by
chemical toxins as CO.
∙ Suppurative Myocarditis: (rare)
- occurs in the course of septicemia or pyemia.
- Focal suppuration occurs in the interstitial tissue of the heart.
- Muscle fibers show degeneration and necrosis.
∙ T.B Myocarditis: (rare)
- as a part of miliary T.B.
∙ Syphilitic Myocarditis:
- diffuse syphilitic myocarditis.
*****
Pharmacology & Treatment

➢ Management of Heart Failure:
1. Treatment of the underlying cause: medical or surgical.
2. Positioning: semi-upright position.
3. Rest: strict bed rest in severe cases.
4. Oxygen: to relieve dyspnea and cyanosis.
5. Sedation: phenobarbitone or chloral hydrate.
6. Diet: high caloric low sodium diet, restricted fluid.
7. Treatment of associated respiratory infections with appropriate antibiotics.
8. Correction of metabolic abnormalities: hypoglycemia, hypocalcemia,
metabolic acidosis,..
9. Treatment of anemic heart failure: frequent small volumes of packed RBCs
(slowly administered)
10. Treatment of polycythemia: partial exchange transfusion.
11. Medications: - Digitalis - α and β adrenergic agonists
- Diuretics - Afterload reducing agents
- Phospho-diesterase inhibitors
- Chronic treatment with β adrenergic blockers
I. Digitalis Digoxin is the usually used.

- It is the most important inotropic drug.
∙ Dosage:
- Loading
Oral digitalization: - Premature: ...................... 0.02 mg/kg
- Neonates: .….................... 0.02 – 0.03 mg/kg
- Infants & Children: …..... 0.025 – 0.04 mg/kg
- Adolescent & Adult: ….... 0.5 – 1 mg/kg
I.V digitalization: 75 % of the oral dose
The initial loading dose is divided as the following:
50 % at first - 25 % after 8 hours - 25 % after another 8 hours
- Maintenance:
¼ of the oral digitalization dose 0.005 – 0.01 mg/kg/day
in 2 divided doses, orally, started 12 hours after the full digitalization dose.
The I.V dose is 75% of the oral dose.
∙ Toxicity:
- Anorexia, nausea, vomiting, diarrhea, headache, dizziness, visual disturbances
- Arrhythmia
- ECG changes: prolonged P-R interval, depressed S-T segment, inversion of the
T wave.
II. α and β adrenergic agonists I.V only

1. Isoproterenol:
- Action: positive central inotropic effect & peripheral vasodilator effect ….
decreasing afterload.
- Dose: 0.03 – 0.05 µg/kg/min. continuous I.V infusion.
2. Dopamine:
- β adrenergic agonists.
- Dose: 2-10 µg/kg/min. continuous I.V infusion.
3. Dobutamine: 2-20 µg/kg/min. continuous I.V infusion.
4. Epinephrine:
- Action: α and β adrenergic agonist.
- Dose: 0.01 – 0.1 µg/kg/min. I.V infusion.
5. Norepinephrine: 0.1 – 2 µg/kg/min. I.V infusion.
III. Diuretics
- Diuretics interfere with water and sodium reabsorption → ↓ blood volume →
↓ pulmonary flow overload → ↓ ventricular filling pressure.
1. Furosemide:
- Dose: initial I.V or I.M dose 1-4 mg/kg/dose, until clinical improvement,
then, a chronic oral course of 1-4 mg/kg/day, 1-4 times/day.
- Adverse effects: hypokalemia, hyponatremia, alkalosis, ototoxicity.
2. Chlorothiazide:
- Dose: 20-40 mg/kg/day in divided doses.
It is used in less severe cases of chronic congestive heart failure.
- Adverse effects: hypokalemia, hypercalcemia, hyperuricemia, hyperglycemia.
N.B: Furosemide and chlorothiazide interfere with Cl reabsorption, furosemide
at the level of ascending loop and chlorothiazide at distal tubules.
3. Spironolactone:
- K retaining diuretic. It inhibits aldosterone leading to potassium retention.
- Dose: 1-3 mg/kg/day in 2-3 divided doses.
- Adverse effects: hyperkalemia.
4. Bumetanide:
- Dose: I.V: 0.01 – 0.1 mg/kg/dose
Oral: 0.0005 – 0.1 mg/kg/day in 3-4 divided doses
- Adverse effects: hypokalemia, hyperuricemia, hyperglycemia.
IV. Afterload Reducing Agents (vasodilators) including ACE inhibitors.

- They decrease ventricular afterload through decreasing peripheral vascular
resistance. This improves myocardial contractility.
1. Nitroprusside:
- Dose: 0.5 – 8 µg/kg/min. Continuous I.V infusion.
2. Hydralazine:
- Dose: initial I.V or I.M: 0.1 – 0.5 mg/kg/dose
in chronic oral use: 0.25 – 1 mg/kg/dose every 6-8 hours.
3. Captopril: (ACE inhibitor)
- inhibits the production of angiotensin II leading to arterial and venous
vasodilation with subsequent decrease in preload and afterload.
- inhibits aldosterone secretion.
- Dose:
- Premature: 0.01 mg/kg/dose
- Infants: 0.1-0.5 mg/kg/dose every 8-12 hrs (max. 4 mg/kg/day)
- Children: 0.1-2 mg/kg/day every 8-12 hrs.
Side effects:
- Hypotension: weakness, dizziness, syncope.
- Rash (maculopapular) - Fetal toxicity.
- Neutropenia. - Renal toxicity (proteinurea)
- Chronic cough (20% of cases)
4. Enalapril: (long-acting ACE inhibitor)
- Dose: 0.08-0.5 mg/kg/dose every 8-12 hrs (max. 0.5 mg/kg/day)
5. Nesiritide:
- Dose : 0.001-0.03 µg/kg/min. I.V.
6. Nitroglycrine:
- Dose: 0.25-5 µg/kg/min. I.V.
7. Prazosin:
- Dose: 0.005-0.025 mg/kg/dose every 6-8 hrs.
V. Phosphodiesterase Inhibitors
- Milrinone.
- Amrinone.
VI. Chronic treatment with β adrenergic blocker

- They are used for chronic treatment of heart failure, not in the acute phase.
1. Metoprolol
2. Carvedilol
*****
Digitalis (Digoxin)
The most important inotropic drug
∙ Mechanism of action:
- It inhibits Na-K ATPase in myocardial cells, increasing intracellular Calcium.
∙ Effects:
i. increases the myocardial contractility and Co & systolic B.P:
- This improves the general condition and the renal blood flow, which results in
diuresis and subsequent decrease in the venous pressure and improvement of
pulmonary and systemic congestion symptoms and signs.
ii. increases the excitability of atria and ventricles (arrhythmia in overdose).
iii. slows the rythmic S.A node, i.e: slows the heart rate.
iv. slows the conduction in the A.V node, which protects the ventricles in atrial
arrhythmia.
v. increases the mechanical efficacy of the heart.
vi. Diuretic effect through improving of the renal circulation.
vii. ECG changes: - shortening of the systole. - prolongation of P-R interval.
- depression of S-T segment. - inversion of T-wave.
∙ Indications:
1) Congestive heart Failure: vagometric (decreases HR, suppresses A.V conduction)
- It is more effective in the left side HF the than the right side HF.
2) Control of supraventricular Arrhythmias:
as it slows the conduction at A.V node and protects ventricles.
- Paroxysmal atrial tachycardia.
- Atrial flutter and fibrillation.
- Prevention of paroxysmal ventricular tachycardia.
∙ Contraindications:
a)Absolute contraindications:
- Digitalis toxicity.
- Paroxysmal ventricular tachycardia (PVT): as it causes fatal ventricular
tachycardia.
- Obstructive lesions: such as TOF, hypertrophic cardiomyopathy.
- With some drugs as adrenaline, ephedrine, calcium which sensitize the
myocardium to digitalis increasing the liability to digitalis toxicity. And Atropine
counteracts digitalis effect.
b) Relative contraindications:
- Ventricular extrasystole:…may lead to ventricular tachycardia and fibrillation
- Partial heart block: … may lead to complete heart block.
- Nodal arrhythmia: … AVN ryhthmicity.
- Peptic ulcer:.. as it increases the vagal tone leading to hyperacidity.
∙ Dosage: see above (p.5)

- oral digitalization: 0.02 – 0.04 mg/kg.
50% of the dose initially, 25% after 8 hrs, 25% after the next 8 hrs.
I.V digitalization is 75% of the oral digitalization dose.
- Maintenance: oral dose is 25% of the oral digitalization dose
(0.005-0.01 mg/kg/d)
I.V maintenance dose is 75% of the oral maintenance dose.
∙ Digitalis Toxicity:
- Clinical signs: anorexia, nausea, vomiting (bad for CHF), diarrhea, headache.
- CNS disturbances: dizziness, visual disturbances, giddiness, delirium.
- Heart: arrhythmias??.. premature ventricular contractions and ventricular
arrhythmia especially ventricular fibrillation.
- ECG: shortening of the diastole, prolongation of P-R interval, S-T segment
depression, T wave inversion.
N.B: Toxicity is diagnosed when serum level is associated with clinical
manifestations and ECG findings.
Management of digitalis toxicity:

1. A delay in administration of the next dose or dosage reduction.
2. Serum K & Ca should be monitored as hypokalemia and hypercalcemia
exacerbate toxicity.
3. Stoppage of the diuretic therapy.
4. If there is hypokalemia, give oral potassium.
5. Avoid hypercalcemia.
6. Treatment of arrhythmias by:
- antiarryhthmic drugs: verapamil, lidocaine, atropine in case of bradycardia,
phenytoin.
- digoxin antidote “digoxin immune fab”.
*****
Antihypertensive Drugs
I. Arterial vasodilators:
hydralazine, Nitroprusside, Minoxidil.
II. Adrenergic blockers:
- α-blockers: phentolamine, phenoxybenzamine, prazocin.
- β-blockers: esmolol, propranolol, atenolol.
- α and β blockers: labetalol.
- CNS α2 agonists: clonidine.
III. Renin-Angiotensin Inhibitors:
captopril, Enalaprilat, Enalapril
IV. Calcium Channel blockers:
Nifedipine, Nicardipine, Amlodipine
V. Diuretic Agents:
Hydrochlorothiazide, Furosemide, Bumetanide
****
I. Arterial Vasodilators
1. Hydralazine:
∙ Action: it relaxes the arteriolar smooth muscles.
∙ Dose: I.V 0.1-0.4 mg/kg/dose every 4-6 hrs
P.O 0.25-1 mg/kg/dose every 6-12 hrs (max.200mg/day)
∙ Side effects: tachycardia, nausea, and drug-induced lupus
2. Nitroprusside:
∙ Action: arterial and venous dilatation.
∙ Dose: 0.3-8 µg/kg/min. I.V infusion.
∙ Side effects: of thiocyanate production.
3. Minoxidil:
∙ Action: arteriolar dilatation.
∙ Dose: initially 0.1-0.2mg/kg/24 hrs, increased gradually to 0.25-1mg/kg/day.
∙ Side effects: hypertrichosis, fluid retention.

II. Adrenergic Blockers

1. α-blockers:
Side effects: tachycardia, nasal congestion, dizziness.
∙ Phentolamine: 0.05-0.1 mg/kg/dose I.V every 1-2 hrs (max. 20mg ...)
- S.E: tachycardia, nasal congestion, chest pain.
∙ Phenoxybenzamine: 0.2 mg/kg/d.. orally every 8-12 hrs
- S.E: nasal congestion, dizziness, …..
∙ Prazosin: 0.005-0.1 mg/kg/dose orally every 6-12 hrs
- S.E: orthostatic hypotension.
2. β-blockers:
Side effects: bronchospasm, hypotension, bradycardia, hypoglycemia.
∙ Esmolol: 50-300 µg/kg/min. I.V
∙ Propranolol: 0.01-0.1 µg/kg/dose I.V, then 0.5-8 µg/kg/24 hrs orally
S.E: vivid dreams.
∙ Atenolol: 1-2 mg/kg/24 hrs orally
3. α and β blockers:
S.E: orthostasis, dizziness, bronchospasm.
∙ Labetalol: bolus 0.2-1 mg/kg/dose followed by 0.25-2 mg/kg/hr infusion,
then 1-3 mg/kg/24 hrs orally.
4. CNS α2 agonists:
S.E: sedation, constipation, rebound withdrawal hypertension.
∙ Clonidine: 0.005-0.025 mg/kg/24 hrs orally (max. 0.9 mg/24 hrs)
III. Renin-Angiotensin Inhibitors

∙ Captopril:
- S.E: proteinuria, neutropenia, chronic cough, rash. (dose: see above)
∙ Enalaprilat:
- S.E: transient hypotension.
- Dose in children: 0.005-0.01 mg/kg/dose I.V over 5 min. every 8-24 hrs
∙ Enalapril:
- S.E: hypotension.
- Dose: 0.1-0.5 mg/kg/24 hrs P.O every 12-24 hrs
IV. Calcium Channel Blockers

∙ Nifedipine:
S.E: facial flushing and tachycardia.
Dose: (in children) 0.25-0.5 mg/kg/dose every 4-6 hrs (max. 1-2mg/kg/d.)
∙ Nicardipine:
- S.E: tachycardia, hypotension, headache.
- Dose: 1-3 mg/kg/min. I.V infusion.
∙ Amlodipine:
- S.E: edema, dizziness, flushing, palpitation.
- Dose: 0.1-0.6 mg/kg/day , orally
V. Diuretic
hydrochlorothizide, furosemide, bumetanide. (see above)
*****
Treatment of Hypertension
I. Mild hypertension:
- Only diuretics: Chlorothiazide, Furosemide.
II. Moderate hypertension:
- Diuretics plus: vasodilator (as hydralazine) or beta blockers (as propranolol,
labetalol, metoprolol).
III. Severe hypertension:
- Combination of: beta blockers, vasodilators and diuretics.
Antiarrhythmic Drugs
Classes:
Classes
I. Na channel blockers: IA, IB, IC
II. β adrenergic blockers
III. K channel blockers
IV. Ca channel blockers

Class I
Na channel blockers – prolong repolarization
Class I A
Quinidine, Procainamide, Disopyramide
1. Quinidine:
∙ Indications: SVT, VT, AF, Atrial flutter.
∙ Dose: 20-60 mg/kg/24 hrs every 6 hrs
∙ S.E: - development of arrhythmia “torsades de pointes”
- Nausea, vomiting, diarrhea, fever.
- Cinchonism: blurred vision, headache, disorientation.
- ECG: QRS, PR prolongation, A.V block, Asystole.
- Thrombocytopenia, haemolytic anemia, SLE.
- Exacerbation of periodic paralysis.
∙ Drug interaction: enhances digitalis effect by decreasing its renal excretion.
Prolongs PPT when given with warfarin.
2. Procainamide:
∙ Indications: as quinidine
∙ Dose: 15-50 mg/kg/24 hrs every 4-6 hrs
∙ S.E: as quinidine plus:
agranulocytosis, prolongation of Q-T interval.
∙ Drug interaction: toxicity with amiodarone and cimetidine.
3. Disopyramide:
∙ Indications: as quinidine except VT.
∙ Dose: <2 yrs: 20-30 mg/kg/day
2-10 yrs: 9-24 mg/kg/day
≥ 11 yrs: 5-13 mg/kg/day
∙ S.E: anticholinergic effects (urinary retention, blurred vision, dry mouth)
QT, QRS prolongation, agranulocytosis, hepatic toxicity, hypoglycemia,
psychosis, torsades de pointes.
Class I B
Lidocaine, Mexilitene, phenytoin

1. Lidocaine:
∙ Indications: Premature ventricular contractions (PVC), ventricular
tachycardia and fibrillation.
∙ Dose: Loading 1 mg/kg repeated every 5 min. for 2 times
Maintenance 20-50 µg/kg/min. infusion
∙ S.E: confusion, convulsion, coma, A.V block, asystole, respiratory failure
∙ Drug interaction: propranolol and cimetidine increase toxicity.
2. Mexilitene:
∙ Indications: VT, PVC ∙ Dose: 6-15 mg/kg/ 24 hrs every 8 hrs
∙ S.E: GIT upset, skin rashes, neurologic...
∙ Drug interaction: cimetidine.
3. Phenytoin:
∙ Indications: digitalis toxicity.
∙ Dose: Loading 10-15 mg/kg over an hour
Maintenance 3-6 mg/kg/24 hrs every 12 hrs
∙ S.E: rash, gingival hyperplasia, ataxia, lethargy, vertigo, tremor, macrocytic
anemia, bradycardia with rapid pulse.
∙ Drug interaction: amiodarone, oral anticoagulants, cimetidine and nifedipine
increase toxicity.
Class I C
flecainamide, propofenone
1. Flecainamide:
∙ Indications: SVT, atrial tachycardia, VT.
∙ Dose: 3-10 mg/kg/day every 8 hrs.
∙ S.E: blurred vision, nausea, decrease in contractility.
∙ Drug interaction: amiodarone increases toxicity.
2. Propofenone:
∙ Indications: SVT, atrial tachycardia, AF, VT
∙ Dose: Loading Maintenance
∙ S.E: hypotension, decrease in contractility, hepatic toxicity, parasthesia.
∙ Drug interaction: increases digitalis level.
Class II
β Blockers
Propranolol
∙ Indications: SVT, PVCs, long QT syndrome.
∙ Dose: Loading 0.1-0.15 mg/kg I.V. over 5 min.
Maintenance 1-4 mg/kg/day every 6 hrs
∙ S.E: bradycardia, bronchospasm, hypoglycemia, hypotension, heart block, HF,
loss of concentration or memory.
∙ Drug interaction: if it is used with disopyramide or verapamil, it precipitates
heart failure.
Class III
K channel blockers – prolong repolarization
Amiodarone
∙ Indications: drug resistant SVT, JET, VT
∙ Dose: I.V Loading: 2.5-5 mg/kg over 30-60 min.(can be repeated up to 3 times)
then: 2-10 mg/kg/day as a single dose
oral loading: 10 mg/kg/day in single or two divided doses for 4-14 day,
reduced to 8 mg/kg/day for several weeks. If no recurrence, reduce the dose to
2-5 mg/kg/day for 5-7 days/week.
∙ Contraindications: severe sinus node, A.V block without pacemaker.

∙ S.E: hypo- or hyperthyroidism, elevated TG, hepatic toxicity, pulmonary
fibrosis.
∙ Drug interaction: digoxin, procainamide, quinidine, warfarin, phenytoin.
Class IV
digoxin, verapamil, adenosine
1. Digoxin:
∙ Indications: SVT, atrial flutter, AF.
2. Verapamil: (Ca channel blocker)

∙ Indications: SVT
∙ Dose: Loading I.V 0.1-0.2 mg/kg every 2 hrs twice.
Maintenance 2-7 mg/kg/day every 8 hrs.
∙ Contraindications: not for use in infants, VT, severe HF, AF with WPW.
∙ S.E: bradycardia, asystole, P-R prolongation, A-V block, hypotension, CHF.
∙ Drug interaction: - if it is used with beta blockers, it exacerbates CHF.
- increases digoxin level and toxicity.
3. Adenosine: (purinergic agonist)

∙ Dose: Loading 50-300 µg/kg given by rapid I.V push.
begin with 50 µg/kg and increase by 50-100 µg/kg/dose if no effect.
*****

Basics for Egyptian Fellowship of Pediatrics (step 1) Renal
Renal System

Embryology
• Development of the renal and genital systems is intimately associated.
• The urinary system develops before the genital system.
• 3 successive kidney systems develop:
- pronephroi (non-functional)
- mesonephroi (temporari excretory organ)
- metanephroi (permanent kidney)
• The metanephroi develop from 2 sources:
- metanephric diverticulum & metanephric blastema.
- metanephric diverticulum gives rise to: ureter, renal pelvis, calices and
collecting tubules.
- metanephric blastema gives rise to: metanephric mass of mesenchyme
which gives the nephrons.
• At first, the kidneys are located in the pelvis, but they gradually shift position
to the abdomen.
• The urinary bladder develops from the urogenital sinus and the surrounding
splanchnic mesenchyme.
N.B: the intermediate mesoderm gives .. and the trigon of urinary bladder.
the endoderm gives the rest of urinary bladder and urethra.
➢ Congenital Anomalies of the kidney:
1) Dysplasia:
- Multiple cystic dysplasia. - Obstructive, e.g: post. urethral valve.
- Prune belly syndrome (dilated non-obstructed urinary tract, bilateral cryptorchidism
and deficient abdominal musculature). - Isolated.
2) Cystic kidney disease:
- AR polycystic kidney disease. - AD polycystic kidney disease.
- Familial juvenile nephronophthisis. - Medullary sponge kidney.
3) Obstructive uropathy without dysplasia:
- PUJ obstruction & VUJ (vesico-ureteric junction) obstruction.
4) Others: VUR, agenesis, duplication anomalies, ureterocele, ectopia/fusion
anomalies.
➢ Congenital Anomalies of urinary bladder:
- failure of obliteration of urachus, resulting in urachal fistula opening in the
umbilicus.
- Recto-vesical fistula due to incomplete uro-rectal septum.
- Urachal cyst: due to local failure of obliteration.
- Ectopia vesica: due to failure of formation of the anterior wall of the urinary
bladder and the anterior abdominal wall below the umbilicus.
- Abnormal termination of the ureter: in rectum, vagina or urethra.
N.B: The urachus is a tubular structure extending from the apex of urinary
bladder to the umbilicus. It becomes obliterated after birth forming the median
umbilical ligament.
➢ Hypospadius:
- The urethra opens in the under surface of the penis.
- It is due to failure of fusion of edges of the urethral groove.
- It is 4 types (acc. to opening site):
a. Glanular: urethral orifice opens on the ventral surface of the glans penis.
b. Penile:.. opens in the ventral surface of the body of the penis (a&b are 80%).
c. Penoscrotal:.. at the junction of the penis and scrotum.
d. Perineal:.. located between the non-fused scrotum (where the labio-scrotal
folds fail to fuse).
➢ Epispadius:
- The urethra opens on the dorsal surface of the penis.
- It is often associated with extrophy of the bladder.
➢ Posterior urethral valve:
- It occurs only in males, and it is the commonest cause of bladder outlet
obstruction.
- Prenatal diagnosis may allow early intervention, and thereby salvage renal
function.
- 50% of babies not diagnosed prenatally will present with symptoms in the first
year of life.
- The prenatal ultrasound findings of hydronephrosis, megaureter, and
oligohydramnios are characteristic.
- After birth, if renal function is good, cystoscopy and diathermy of the valve
may be carried out.
- If renal functions are impaired:... vesicotomy.
Physiology
Functions of kidney
I. Glomerular filtration:
- involves passage through 3 layers:
1. capillary endothelium lining the glomerulus.
2. glomerular basement membrane.
3. epithelial layer of Bowman's capsule.
- Renal blood flow (RBF) = 20-25% of the cardiac output = 1200 ml/min.
- Glomerular filtration rate (GFR): is the plasma volume filtered across
glomeruli to Bowman's capsule per unit time = 20% of RBF = 120 ml/min =
180 L/day.
- Renal clearance: is the volume of plasma from which all of a given substance
is removed per minute by the kidney.
Clearance = amount excreted / min.
plasma conc. of substance x
GFR = Ux V Ux: urine conc. V: urine vloume Px: plasma conc.
Px
Creatinine clearance = 140-age (in yrs) X wt (x 1.2 in male and x 0.8 in female)
72 X serum creatinine
II. Function of proximal convoluted tubules:
- Iso-osmotic reabsorption 65% of glomerular filtration, including glucose, Na,
K, amino-acids, proteins, vitamins via active transport.
III. Function of loop of Henle:

- 25% of filtered Na is absorbed at the thick ascending limb mostly through
channel mediated transport, leading to reabsorption of Na, K, Cl.
- 15% of filtered water is removed by the loop of Henle.
N.B: Fluids entering loop is isotonic, at tip of the loop is hypertonic and leaving
the loop hypotonic.
IV. Distal convoluted tubules:

- Reabsorb 5-10% of Na and 3% of HCO3.
- relatively permeable to water.
- late distal segment is a site of ADH and aldosterone action.
V. Endocrine Functions:
1) Renin: decrease in the intravascular volume (as in hge or dehydration)
stimulates renin secretion from juxta-glomerular cells, with the following
effects:
- constriction of the efferent arterioles to maintain GFR.
- release of aldosterone from adrenal cortex.
- increase the release of ADH from the posterior pituitary.
- Thirst.
- Inotropic myocardial stimulation and systemic atrial constriction occur.
The opposite occurs in case of fluid overload.
2) Aldosterone:
- promotes Na and water reabsorption in the distal convoluted tubules and the
collecting duct, where Na is exchanged for K and H ions by a specific cellular
pump.
3) Atrial Natriuretic Peptide (ANP):
- is released when atrial pressure increases as in heart failure or fluid overload.
- it promotes loss of Na, Cl and water through increasing GFR.
4) ADH:
- increases the water permeability of the distal tubules and the collecting ducts
with increase in urine concentration.
- in contrast, when ADH release is inhibited, dilution of urine is the result.
5) 1,25 hydroxy vit.D: promotes Ca absorption from gut.
6)Erythropoietin: released from fibroblast-like cells in cortical interstitium in
response to hypoxia and anemia.
7) PG E2 , A2 and bradykinin.
Measurement of Renal Functions

1) Serum Creatinine:
- indirect estimate of renal function using a product of creatinine metabolism.
2) Creatinine Clearance:
- as reflection of GFR, can be estimated by the following formulas:
GFR = urinary creat. (Ucr) X urine flow rate (Vu)
plasma creatinine conc. (Pcr)
or = (140-Age) X 1.2 X wt (- 0.05 in female) Normally = 75 – 120 ml/min.
Pcr
3) Blood Urea Nitrogen (BUN):
-not accurate and should not be used alone as a measurement of kidney
function.
ADH (Vasopressin)
- synthesized in supra-optic and paraventricular nuclei of hypothalamus.
- transported along nerve axons to pituitary and released by neurophysins.
- the active form is arginine vasopressin.
• Control of secretion: ADH can be released in response to:
a. increase in blood osmolality, which stimulates osmoreceptors in the anterior
hypothalamus.
b. decrease in fluid volume, which decreases tension on stretch receptors in the
left atrium, venae cavae, great pulmonary vessels, carotid sinus and aortic arch.
• Syndrome of inappropriate ADH secretion (SIADH):

1. Increase in pituitary ADH:
- Hypoadrenalism and stress.
- Drugs: nicotine and barbiturates.
- Lung diseases: pneumonia, T.B, pleural effusion, positive mechanical
ventilation.
- Intracranial disease: head injury, stroke, encephalitis.
- Syndromes: acute intermittent porphyria.
2. Increased sensitivity to ADH: carbamazipine.
3. Ectopic source of ADH: bronchogenic carcinoma.
Criteria for diagnosis of SIADH:
N.B: water retention occurs with increased ECF volume. However, oedema
does not due to inhibition of aldosterone secretion, which causes increase
urinary Na excretion.
1. Hyponatremia and decreased plasma osmolality.
2. Urinary Na output is high at 50 mmol/day.
3. Urine osmolality is inappropriately high in relation to serum osmolality.
4. No evidence of hypovolemia.
5. Increasing plasma osmolality in response to decrease of water intake.
• Causes of ADH deficiency:

1. Cranial Diabetes Insipidus (D.I):- inherited autosomal dominant or
recessive.
- acquired: hypothalamic disorder.
2. Nephrogenic D.I: - inherited: SLR
- acquired: chronic renal disease, lithium, osmotic
diuresis.
3. Primary polydypsia with psychotic disorders.

Pathology
Pathological Changes in The Nephron
Glomeruli Tubules Interstitium
∙ Basement membrane deposition ∙ Atrophy. ∙ Fibrosis.
and thickening of epith. or
endothelium. ∙ Deposition. ∙ Infiltration by inflammatory
∙ Focal or segmental proliferation cells.
for some cells as mesangial cells. ∙ Casts
∙ Infiltration by inflammatory cell.
∙ Sclerosis.
➢ Glomerular diseases pathogenesis:

- Glomerular injury may result from immunologic, genetic or coagulation
disorders.
- The immunologic injury is the most common cause and results in
glomerulonephritis.
- There appears to be 2 mechanisms of immunologic injury:
1. Glomerular deposition of circulating Ag-Ab immune complexes, where these
complexes accumulate in GBM and activate complement system leading to
immunologic injury.
2. Interaction of antibodies with local antigen 'in situ': anti-GBM antibodies
disease is an example of in situ Ag-Ab reaction.
➢ Response of glomeruli to diseases:
- The glomerulus may be injured by several mechanisms, but has only a limited
number of histopathologic responses, i.e: different disease states may produce
similar microscopic changes.
1. Cellular proliferation: It occurs in most forms of glomerulonephritis. The
glomerulus shows increase in number of endothelial, epithelial and mesangial
cells. It is frequently associated with increase in mesangial matrix and
narrowing of lumena of glomerular capillaries, ending in renal insufficiency.
- It may be generalized involving all glomeruli or focal involving only some..
- Within the same glomerulus, proliferation may be diffuse involving all parts of
the glomerulus or segmental affecting some areas.
2. Crescent formation in Bowman's space “capsule”:
- It develops in several forms of GN termed rapidly progressive.
- It is due to proliferation of the parietal cells and deposition of fibrin in
Bowman's space.
- The crescent is subsequently invaded by connective tissue leading to
glomerular obsolescence.
3. Thickened appearance of glomerular basement membrane: may results from:
- True increase in width of membrane with increase in deposition of B.M
substances itself as in membrane glomerulopathy, or deposition of foreign
substances (such as Ig, Ag-Ab complexes, fibrin) as seen in SLE.
- Interposition of mesangial cells and matrix into subendothelial space between
the membrane and endothelial cells as in type 1 membranoproliferative GN.
4. Sclerosis: presence of scar tissue within the glomerulus.
5. Tubulointerstitial fibrosis: it is present in all patients with glomerular disease
who develop a progressive renal injury. Fibrosis and matrix deposition occurs
with subsequent destruction of renal tubules and peritubular capillaries.
6. Leucocytic infiltration: it may be seen in some inflammatory diseases of
glomeruli, in the glomerular capillaries of Bowman's capsule.
7. Hyalinization: accumulation of homogenous esinophilic substance. It denotes
irreversible injury to structure and function of glomeruli.
➢ Classification of glomerular diseases:

- The pathological lesions seen in the glomerular diseases are divided into:
A. Nephritic syndrome: glomerulonephritis characterized by inflammatory
lesions in glomeruli, and clinical picture of hematuria, azotemia and
hypertension.
B. Nephrotic syndrome: heavy proteinuria, hypoalbuminemia, edema,
hyperlipidemia.
∙ Types of nephritic syndrome:

- Acute post-streptococcal GN. - Rapidly progressive GN.
- Chronic GN. - Focal GN.
∙ Another classification of nephritic syndrome:
a. Primary: - Acute post-streptococcal GN (diffuse, immune complex GN).
- Focal proliferative GN.
- Rapidly progressive GN(crescentic).
- Membrano-proliferative GN.
- IgA nephropathy (Berger's disease).
b. Secondary:
- SLE.
- Good pasture’s syndrome.
- IgA nephropathy (Henoch-Schonlein purpura)
- Hemolytic uremic syndrome.
Acute post-streptococcal GN
It is an AGN believed to be mediated by immune complexes.
∙ Light microscopy (L/M):
- all glomeruli appear enlarged and relatively bloodless and show diffuse
mesangial cells proliferation with an increase in mesangial matrix.
- Crescents and interstitial inflammation may be seen in severe cases.
∙ Electron microscopy (E/M):
- deposits are observed on the epithelial sides of the glomerular basement
membrane (subepithelial humps).
∙ Immunofluorescence microscopy(IF/M):
- Ig and complement deposits in the glomerular basement membrane and
mesangium.
Systemic lupus nephritis
- WHO classification is based on L/M, E/M, IF/M

∙ WHO class I nephritis: no histopathologic abnormalities.
∙ WHO class II nephritis: mesangial lupus nephritis (mild IIA, moderate IIB).
∙ WHO class III nephritis: focal segmental lupus nephritis. Focal and
segmental mesangial proliferation, crescent formation, glomerular and
necrosis.
∙ WHO class IV nephritis: diffuse proliferative lupus nephritis.
∙ WHO class V: membranous lupus nephritis.
Rapidly progressive (crescentic) GN
- Type I: anti-GBM (20%)

- Type II: immune complex nephropathies. (20%)
- Type III: ANCA (60%)
∙ L/M: hypercellular glomeruli, with moderate proliferation of endothelial and
mesangial cells.
- the characteristic lesion is proliferation of epithelial cells of Bowman's
capsule to form “crescents” in most glomeruli. These crescents forms rapidly
and appears early in the diseases.
∙ E/M: Ig and complement are deposited in the basement membrane.
Focal proliferative GN
- It is similar to acute post-streptococcal GN, but fewer glomeruli are affected.
Membrano-proliferative GN
- By light microscopy: thickened basement membrane (tram-track appearance),

due to proliferation of mesangial cells which interpose between endothelium
and basement membrane.
The Nephrotic Syndrome

∙ These are group of kidney diseases of variable causes and pathogenesis, but
showing common clinical picture (proteinuria, edema, hypoalbuminemia,
hyperlipidemia).
∙ Pathologically:
Glomeruli are primarily affected in all nephrotic syndrome diseases, showing:
- loss of foot processes. - thickening of the basement membrane.
Causes of Nephrotic Syndrome:
I. Idiopathic N.S: - Minimal change disease (lipoid nephrosis)
- Focal segmental glomerulosclerosis
- Membranous nephropathy (Heymann's nephritis)
- Membrano-proliferative
II. Secondary N.S:
- Systemic diseases: DM, SLE, neoplasm.
- Infections: parasitic (malaria, bilharziasis)
viral (HBV, HCV, HIV)
bacteria (strept.)
- Drug-induced: NSAIDs, gold, heroin.
∙ Minimal Change Disease (lipoid nephrosis or foot processes disease) 85%
- L/M: nothing, a minimal increase in mesangial cells and matrix.
- E/M: loss of foot processes of epithelial cells of glomerular capillaries.
- IF/M: typically negative (not diagnostic).
∙ Mesangial proliferation 5%
- L/M: diffuse mesangial cells and matrix proliferation,
- E/M: increase in number of mesangial cells, with effacement (retraction) of
foot processes.
- IF/M: traces to plus 1 mesangial IgM &/or IgA staining.
∙ Focal segmental glomerulosclerosis
- L/M: the majority of glomeruli appears normal, some shows mesangial
proliferation and segmental scarring in one or more lobules “focal sclerotic”,
progressive to involve all glomeruli resulting in renal failure.
- E/M: foot process fusion.
- IF/M: IgM and C3, in areas of segmental sclerosis.
Urinary Tract Obstruction

Causes:
∙ Infundibular:
- congenital. - calculi. - T.B. - traumatic. - postoperative. - neoplasm.
∙ Renal pelvis:
- congenital 'infundibulo-pelvic stenosis'. - T.B. - calculi.
- neoplasm (Wilm's tumor, neuroblastoma).
∙ Uretero-pelvic juction:
- congenital stenosis. - calculi. - neoplasia. - inflammatory.
- T.B. - postoperative. - traumatic.
∙ Ureter:
- congenital obstructive mega ureter. - mid ureteral structure. - ectopia.
- ureterocele. - ureteral valve. - calculi. - postoperative.
- external compression: neoplasm (lymphoma, neuroblastoma, pelvic tumors).
inflammatory (Crohn's disease)
hematoma, urinoma, lymphocele, retroperitoneal
fibrosis
∙ Bladder outlet \ urethra:
- neurogenic bladder dysfunction. - posterior urethral valve.
- urethral stricture (congenital, traumatic) - anterior urethral valve.
- urethral atresia. - calculi. - F.B. - phimosis.
- external compression by a tumor - urogenital sinus anomalies.
Tumors of the Kidney
Pediatric renal tumors represents approximately 7% of all childhood tumors.

∙ Benign tumors:
- Fibroma: in medulla.
- Adenoma: in cortex.
- Hemangioma.
∙ Malignant tumors:
- Primary: Wilm's tumor and hypernephroma (renal cell carcinoma).
- Secondary: carcinoma of lung, prostate, breast.
Sarcoma; osteosarcoma.
Malignant melanoma and choriocarcinoma.
Wilm's Tumor (Nephroblastoma)

It is a complex mixed embryonal neoplasm of the kidney composed of
3 elements: blastema, epithelia and stroma.
Two broad categories of Wilm's tumor are recognized (acc. to histopathology):
1. Favorable form: good prognosis
- It is characterized by blastema, epithelia and stroma devoid of ectopia or
anaplasia.
2. Unfavorable form:
- It is characterized by areas of anaplasia (focal or diffuse) and marked
enlargement of nuclei with hyperchromatism and multipolar mitotic figures.
Origin: it arises from persistent immature cells of the kidney rudiments called
nephrogenic nests.
Age: first 4 years.
Macroscopic: may be bilateral.
- Soft fleshy and homogenous gray in cut section.
- Rapidly growing tumor destroys the kidney tissue and infiltrates the capsule,
then extends to nearby structures.
Microscopic: adenosarcoma
- sarcomatoid elements: short spindle or rounded embryonal cells, striated
muscles, cartilage, bone, myxomatous tissue.
- carcinomatous elements:acini,imperfect tubules and glomerular-like
structures.
Spread:
- Local: to capsule and surrounding tissues.
- Lymphatic: to lumber and para-aortic lymph nodes.
- Blood: rapid spread to lungs, brain and liver.
Staging: I: limited to kidney, can be completely excised with intact capsule.
II: extends beyond the kidney but can be excised.
III: residual extension of the tumor in the abdomen after excision.
IV: haematogenous spread, frequently to lungs (bilaterally).
V: bilateral renal involvement.

Treatment of Nephrotic Syndrome
➢ Treatment of idiopathic nephrotic syndrome:
syndrome
- indication of hospitalization is severe edema including pleural effusion, ascitis
or marked genital edema.
I. Observation: - Temperature (infection) - Weight - Blood pressure.

- urine: volume, specific gravity, daily protein excretion.
II. Diet: - sodium restriction.

- potassium: in sufficient amount when diuretics are used.
- fluids: are not restricted except if there is increase in weight.
- proteins: high intake.
- carbohydrates: high intake to prevent gluconeogenesis.
- fats: reduced (nauseating).
III. Drugs:
1. Antibiotics: - prophylactic to guard against infections: oral penicillin.
- therapeutic: aggressive broad spectrum antibiotic therapy in
case of infection (avoid nephrotoxic drug).
2. Diuretics: avoid aggressive diuretic therapy as it can result in:
hypovolemic shock or hemoconcentration with venous and arterial thrombosis.
- mild to moderate edema: chlorothiazide 10mg/kg/dose every 12 hours.
- severe edema: metolazone (acts on proximal and distal tubules)
0.1mg/kg/dose orally twice daily followed by
furosemide (loop diuretic) 30 minutes later 1-2mg/kg/dose every 12 hours I.V.
- In case of resistance to oral diuretics, intravenous agents may be effective.
- Kcl should be added when diuretics are given.
3. Salt-poor human albumin 25%:
- used in marked hypoproteinemia and severe edema.
- dose: 0.5mg/kg/12hrs I.V over 2 hours followed by furosemide 1mg/kg I.V to
guard against circulatory overload, hypertension and congestive heart failure.
4. Treatment of hyperlipidemia:
- 3-hydroxy 3-methylglutaryl coenzyme A reductase- inhibiting drugs.
5. Corticosteroid Therapy:
∙ Initiation of steroid therapy may be delayed few days to:
- confirm diagnosis by laboratory studies.
- allow time to diuretic therapy to decrease edema.
- exclude latent infection, as UTI and T.B.
∙ Prednisone:
Prednisone
- Dose: 60mg/m2/day (max.: 80mg) divided into 2-3 doses after feeding.
- Duration: daily for at least 4-6 consecutive weeks (6w are preferred due to lower
incidence of relapse), until urine becomes free from protein.
∙ Alternate day therapy:
therapy
- After 4-6 week course (after urine becomes free of protein for 3 consecutive
days, a dose of 40 mg/m2 is taken every other day as a single dose with
breakfast
- The alternate day therapy is slowly tapered and discontinued over 2-3 months.
∙ About 80-90% of patients respond to daily steroids therapy within one month.
This is called the initial response, in which patients are classified into:
Group 1: 1 patients will respond without subsequent relapses.
Group 2: 2 patients will respond, but they are infrequent relapsers <4 time in one
year. Therapy is initiated when relapse occurs.
Group 3: 3 patients initially respond, but are frequent relapsers 4 times or more
in
1 year. They are steroid dependent.
dependent In this group, Cyclophosphamide should
be considered. The alternate day therapy should be continued with
cyclophosphamide (2-3 mg/kg/day single dose) for 8-12 weeks.
Side effects of cyclophosphamide are leukopenia and neutropenia, disseminated
varicella infection, hemorrhagic cystitis, sterility.
TLC should be monitored weekly and therapy is stopped if it is below
5,000/mm3.
∙ Steroid resistant type or initial non-responders (after 8 weeds steroid
therapy):
- Renal biopsy is indicated to determine the aetiology.
- An alternate-day therapy is continued plus:
a. High dose pulse of methylprednisolone 30mg/kg bolus (max. 1000mg), with
the first 6 doses given every other day, followed by tapering regimen over a
period of 18 months.
b. Cyclophosphamide, in selected cases.
c. Cyclosporine (3-6 mg/kg/day every 12 hrs): side effects are hypertension,
nephrotoxicity, hirsutism, gingival hyperplasia.
or Tacrolimus (0.15 mg/kg/day every 12 hrs).
d. ACE inhibitors: reduces proteinuria in steroid-resistant patients.
∙ Renal biopsy is indicated when features that make MCNS unlikely (hematuria,
hypertension, renal insufficiency, hypocomplementemia or age <1yr or >8yrs.
IV. Treatment of end stage renal failure:

- dialysis or renal transplant.
V. Vaccination:
- Polyvalent pneumococcal vaccine.
- Varicella vaccine.
- Annual influenza vaccine.
- Prophylactic VZ Ig should be given to non-immune patients in relapses
exposed to varicella in 72 hours.
➢ Treatment of secondary nephrotic syndrome:

Treatment of the cause.
Treatment of Urinary Tract Infections

➢ Treatment of acute cystitis:
- Treatment can be delayed until the results of culture and sensitivity testing.
- It can be initiated 3-5 days before the availability of the results if symptoms
are severe: - Amoxicillin: 50 mg/kg/day
- Trimethoprime-sulfamethoxazole: oral or I.V
20mg sulfa & 4mg timethoprim per kg/day in 2 divided doses.
It is the treatment of choice if oral route is selected.
- Nitrofurantoin: 5-7 mg/kg/day in 3-4 divided doses.
- Then treatment according to results of culture and sensitivity should be given
regularly for 7-10 days.
➢ Treatment of acute pyelonephritis:

1. Ceftriaxone: 50-75 mg/kg/day max. 2 gm.
2. Ampicillin: 100 mg/kg/day plus Aminoglycosides 3-5 mg/kg/day.
3. Oral 3rd generation cephalosporins, cefixime:
It is the treatment of choice of oral therapy.
- Treatment should be continued for 14 days.
N.B: Alkalinization of urine by sodium bicarb. increases the effectiveness of
antibiotics.
➢ Treatment of chronic pyelonephritis: treatment of HTN e renal

insufficiency
∙ Prophylaxis against re-infection:
- High fluid intake.
- Regular voiding.
- Prevention and treatment of constipation.
- Identification of the predisposing factors to UTI, if recurrence is frequent.
- A urine culture should be obtained a week after termination of antibiotic
therapy to exclude recurrence.
- Follow-up urine culture periodically at 3-month interval.
- Antibacterial prophylaxis in: recurrent UTI, persistent VUR, obstruction,
stone.
Trimethoprime-sulfamethoxazole or nitrofurantoin: 3 rd of therapeutic dose is
given once daily.
Treatment of Enuresis

I. Management of daytime wetting:
1) Encourage the child to go to bathroom whenever he feels urge to urinate.
2) Increase fluid intake at daytime and restrict at night.
3) Stream interruption exercises.
4) Reward the child for being dry.
5) Do not ignore wet clothes. Change it once being wet.
6) Avoid punishment.
7) Stress-related types need sympathy and support.
8) Resistive child:
- discontinue all punishment.
- improve the parent-child relationship.
- increase the child sense of personal responsibility.
II. Management of Nocturnal Enuresis:

1) Fluid restriction after 6 or 7 pm.
2) Adenoidectomy, if the child snores and adenoids are enlarged.
3) Age-related approach to enuresis.
a. 3-6 years: motivation and counseling.
b. 6-8 years: bladder exercise.
c. above 8 years: enuresis alarm - medications.
A. Motivation and counseling:
i. reassurance of parents about immature or small bladder:
- avoid punishment.
- reporting high prevalence of the problem and that many children become dry.
ii. active role:
- help the child take responsibility for the symptom.
- voiding at bedtime and awaken the child few hours after sleeping to void.
iii. positive reinforcement for dry nights.
iv. symptoms removal by demonstrating to the child that dry nights are possible.
B. Bladder exercises:
- Bladder stretching exercise; by holding the urine as long as possible before
voiding.
- Stream interruption exercise: helps increase the ability to withstand bladder
spasms.
C. Enuresis alarms “conditioning therapy”:
- It is indicated in enuretic child over 8 years old after failure of motivational,
counseling and bladder exercises.
D. Medications:
1. Imipramine “Tofranil”:
- Mechanism of action: anticholinergic effect (not used before the age of 6 yrs)
- Dose: 25 mg (6-8 years) - 50 mg (9-12 years) - 75 mg (above 12 years).
- It is given at bedtime until symptoms removal (success rate is 30-60%)
- Side effects: anxiety, insomnia, dry mouth and hepatotoxicity.
2. Anti-diuretic agents: (Desmopressin-Minirin):
- Nasal spray: 10-40 micrograms before going to bed.
- Recently, it is available as tablets 0.2-0.6 mg at bedtime.
- Treatment should be continued for 3-6 months, then taper the dose.
3. Oxybutynin: a pure anticholinergic agent
- It reduces the uninhibited detrusor muscle contraction by direct
anticholinergic effect.
- 5 mg at bedtime at the age of 8 years & 5 mg tds for teenagers.
- Side effects of anticholinergic drugs.
*****

Basics for Egyptian Fellowship of Pediatrics (step 1) GIT
Gastroenterology

Embryology
∙ The primitive gut is recognized at the 4th week of gestation and is composed
of:
- Foregut: pharynx, esophagus, stomach, duodenum to the level of insertion of
the common bile duct.
- Midgut: the rest of small and large intestine to the level of mid-transverse
colon.
- Hindgut: the remainder of the colon and the upper part of the anal canal.
N.B: gut lining is endodermal in origin except the lower part of the anal canal,
which is ectodermal in origin.
Blood supply of the GIT
- Foregut: celiac artery.
- Midgut: superior mesenteric artery.
- Hindgut: inferior mesenteric artery.
Development of the Esophagus
- It is developed from the posterior pharyngeal foregut.

- The trachea is separated from the esophagus by the tracheo-esophageal
septum. Initially, it is short but it rapidly elongates. It reaches the final relative
length by 7th week. Recanalization occurs by about 8th week.
- The intra-abdominal location of the distal esophagus and the lower
esophageal sphincter are important anti-reflex mechanisms.
∙ Congenital Anomalies of the esophagus:
- esophageal atresia. - esophageal stenosis.
- short or long esophagus. - congenital hiatal hernia.
- tracheo-esophageal fistula. - laryngo-tracheo-esophageal cleft.
Esophageal Atresia:
- Blockage of the esophagus.
- in 1/3000 live births, approximately third of them are born prematurely.
- It is associated in 85% of cases with TEF.
- Isolated esophageal atresia may be associated with other congenital
anomalies, such as anorectal atresia and anomalies of the urogenital system.
Causes of esophageal fistula:
- deviation of the tracheo-esophageal septum in a posterior direction leading to
incomplete separation of the esophagus from the trachea.
- Isolated atresia, it is due to failure of recanalization at 8 th weeks.
- A fetus with esophageal atresia is unable to swallow amniotic fluid, so fluid
can not pass to intestine leading to polyhydramnios.
- It is most often associated with VATER/VACTERL anomalies (vertebral, ano-
rectal, trachea, esophagus, cardiac, renal, radial, limbs).
Development of the Stomach
- Around the middle of the 4th week, a slight dilatation indicates the site of the
primordium of stomach.
- A fusiform enlargement, at the 5th week of the caudal or distal part of the
foregut. It soon enlarges and broadens ventro-dorsally.
- During the next 2 weeks, the dorsal border grows faster than the ventral
border, which leads to the greater curvature of stomach.
- As stomach enlarges and acquires its final shape, it slightly rotates 90 o in a
clockwise direction around its longitudinal axis.
Congenital Hypertrophic Pyloric Stenosis (CHPS)
- Incidence: 1:150 male & 1:750 female.
- In infants with this anomaly, there is a marked muscular thickening of the
pylorus (the distal sphincter region of the stomach).
- The circular and to the lesser degree the longitudinal muscles in the pyloric
region are hypertrophied resulting in severe stenosis and obstruction of the
pyloric canal.
- This obstructs the passage of food and stomach becomes distended. The infant
expels the stomach contents in a considerable force ( non-bilious projectile
vomiting).
- It has been associated with: esinophilic gastroenteritis, Apert syndrome,

Zellweger syndrome, trisomy 21.
- There is an association between the use of erythromycin in neonates and
pyloric stenosis. Erythromycin is motilin agonist resulting in strong non-
propagated contractions and consequently hypertrophy of the pylorus.
- I.V prostaglandins may be associated with development of pyloric obstruction.
Development of the small intestine
- Early in the 4th week, the duodenum begins to develop from the caudal or distal
part of the foregut and the cranial or proximal part of the midgut and the
splenich mesenchyme.
- The developing duodenum grows rapidly, forming C-shaped loop that project
ventrally.
- During the 5th to 6th week, the lumen of the duodenum becomes progressively
smaller and is temporarily obliterated.
- Recanalization occurs by the end of the embryonic period.
Developmental Anomalies of the small intestine:
- Atresia, Malrotation.
- Duplication and Meckle's diverticulum.
Intestinal atresia and stenosis:
- Atresia: complete obstruction of the bowl lumen (33% of causes of neonatal
intestinal obstruction).
- Stenosis: partial block of luminal contents.
- Malrotation: incomplete rotation of the intestine during fetal development. The
most common type is failure of the cecum to move into the right bowl quadrant.
Doudenal atresia
- complete occlusion of the duodenal lumen due to failure of recanalization of
the lumen which is completely occluded by epithelial cells.
- the blockage occurs nearly always at the junction of the bile and pancreatic
ducts (hepato-pancreatic ampulla).
- It may occur as an isolated anomaly. However, other congenital anomalies are
often associated: C.V anomalies, malrotation, rectal.
- About 3rd of the affected infants have Down syndrome. Additionally, 20% are
premature.
- Polyhydramnios occurs due to prevention of normal intestinal absorption of
the swallowed amniotic fluid.
Malrotation:
- Incomplete rotation of the intestine during the fetal development.
Non-rotation occurs when the bowls fails to rotate after it returns to the
abdominal cavity. The first and second portion of the duodenum are in their
normal position, but the remainder of the duodenum, jejunum and ileum occupy
the right side of the abdomen while the colon is located on the left side
(abdominal heterotaxia, splenia-polysplenia congenital heart malformation
syndrome.
Intestinal Duplication:
- A rare anomaly that consists of well-formed tubular or spherical structures
firmly attached to the intestine with a common blood supply.
- Duplication can be classified into:
a. localized duplication: occurs due to defect in recanalization of the intestinal
lumen, most commonly in ilium and jejunum.
b. associated with spinal cord defects and vertebral malformations;
hemivertebra and anterior spina bifida.
c. duplication of the colon: It is usually associated with anomalies of the urinary
tract and genetalia.
Sequels of intestinal duplication:
- may cause intestinal obstruction.
- may act as a lead point of intussusception.
- may be a site for a volvolus.
Umbilical hernia, Omphalocele:
- In umbilical hernia, there is a part of intestine covered with greater omentum
and skin herniating outward.
- In omphalocele, a part of intestine covered with skin only.
Abnormal site of cecum and appendix (subhepatic position):
Meckle's Diverticulum:
Origin:
- in the embryo, the ileum is linked to the yolk sac by the vitello-intestinal duct
wich will become atretic.
- If the duct remains patent, a persistent omphalo-mesenteric duct ensues with
entero-cutaneous fistula.
- If the distal umbilical end becomes atretic and closed, and cord is fibrosed, the
result is Meckle's diverticulum.
Site:
- 50 to 75 cm proximal to the ileo-cecal junction.
- it may lead to hernia, intestinal atresia or haemorrhage.

‫صو رة‬
Cyst Vitello-intestinal fistula Meckle's diverticulum
2cm lenghth 2% of people 2 feets from the ileo-cecal valve
Omphalocele:
- A loop of intestine remains inside the umbilical cord at birth due to failure of
reduction of the physiologic hernia.
Congenital Aganglionic Megacolon (Hirshsprung disease)
- absence of the ganglionic cells (Meissner's and Auerbach's plexuses) in the
bowl wall.
- It begins in the internal anal sphincter and extends to involve all the gut, but
mainly the recto-segmoidal region in 75% of cases.
- presented by delayed passage of meconium or chronic constipation.
Imperforate anus
Development of Liver and Biliary System
The liver, gall bladder and biliary duct system arise as hepatic diverticulum
(liver bud) from the caudal or distal part of the foregut early in the middle of the
3rd week.
- Fibroblast growth factors, secreted by the developing heart, interact with
bipotential cells and induce formation of the hepatic diverticulum.
- The hepatic diverticulum enlarges rapidly and divides into 2 parts: the large
cranial part represents the primordium of the liver, while the small caudal part
represents the gall bladder. The stalk of the diverticulum represents the common
bile duct. The stalk (bile duct) connects the hepatic and cystic duct to the
duodenum.
- Bile enters the duodenum through the bile duct after the 13th week, giving the
meconium (the intestinal contents).
- Blood cells, kupffer cells and GI and its cells develop from the mesoderm of
the septum transversum.
Biliary Atresia: failure of recanalization of biliary duct.
- This the most serious anomaly of the extrahepatic biliary system, and occurs in
one of 10,000 to 15,000 live births.
- The most common form (85% of cases) is obliteration of the bile ducts at or
superior to portahepatis.
- It is not a congenital abnormality; as pigmented stool are passed soon after
birth in 20% of cases.
It may be:
- perinatal biliary atresia: due to perinatal infection of reovirus type 3, resulting
in progressive fibrosing obliteration of the extrahepatic ducts.
- Embryonic biliary atresia: it may be the result of mutations in genes
controlling normal bile duct formation or differentiation.
- Other major factors; which may be the role played by genetic predisposition to
autoimmunity.
Accessory hepatic duct: common, without any problem.
Duplication of the gall bladder, without any problem.
Intrahepatic biliary atresia: bile duct inside the liver is not canalized.
Anatomy and Functions of the Liver

Anatomy
Liver lobules:
- The functional unit of the liver is the liver lobule (a central hepatic vein
surrounded by liver cells).
- The hepatocytes are arranged in cords separated by sinusoids.
- The liver lobules are separated by the portal tracts (a branch of hepatic artery,
a branch of portal vein, interlobular bile duct).
The blood supply of the liver:
1. Hepatic artery: from the celiac axis of the aorta.
2. The portal vein: right and left branches ==> liver lobules ==> small
branches ==> to portal tract which empty into intralobular sinusoids.
3. The sinusoids: they empty into the central vein of the lobule to large veins to
the left and right hepatic veins to I.V.C.
The biliary system:
- The liver cells form and secrete bile into bile canaliculi to small intrahepatic
bile ducts to large intrahepatic bile ducts, then to right and left hepatic ducts
which unit to form the common bile duct, which in turn is joined by the cystic
duct to form the common bile duct, and consequently join the main pancreatic
duct, to ampulla of Vater which opens into 2 nd part of duodenum.
Functions of the liver:
1. Nutrition: receives, processes and stores nutrients absorbed from small
intestine, and released on demand.
2. Synthetic function: plasma proteins (albumin, clotting factors, transport
proteins).
3. Immunologic function: transport of Ig and remove Ag by kupffur cells.
4. Haematologic function: synthesis and release of coagulation factors.
5. Detoxification: of exogenous and endogenous compounds.
6. Excretory function: forms and releases bile salts and pigments into small
intestine.
7. Endocrine function: metabolism of insulin, thyroid and steroid hormones.
Physiology
Gut hormones Gut enzymes

Digestion and Absorption Liver Functions
Gut Hormones
- At least, there are 18 hormones that affect most aspects of digestive system
functions and activities of other systems.
- They are peptides, produced by entero-endocrine cells in the digestive tract.
- 4 major regulatory hormones in the gut:
(1) Gastrin:
- Site: from the gastric antrum, G-cells.
- Stimuli for release: distension of the gastric antrum.
Vagal innervation and negative feedback mechanism.
Protein digestive products (amino-acids)
- Action: stimulation of gastric secretion, motility and mucosal growth.
(2) Cholecystokinin (CCK):
- Site: intestinal cells of duodenum and jejunum.
- Stimuli for release: fat, amino-acids and certain cations (Ca, Mg)
- Action: stimulation of pancreatic enzymes secretion and contraction of gall
bladder.
Inhibition of gastric emptying.
(3) Secretin:
- Site: S-cells of the duodenum.
- Stimuli of release: intraluminal acids in the duodenum.
- Action: increase pancreatic and biliary HCO 3 _ secretion.
Inhibition of gastric motility and secretion.
(4) Gastric inhibitory peptide:
- Site: duodenum and jejunum.
- Stimuli of release: fatty acids, amino-acids and carbohydrates.
- Action: inhibition of gastric acid secretion and motility.
Stimulation of insulin secretion.
(5) Other G.I hormones:
Motilin (from duodenum and jejunum): stimulates gastric and intestinal
motility.
Pancreatic polypeptide (from pancreas): inhibits pancreatic enzymes secretion
and relaxes gall bladder.
Vaso-active intestinal peptide (from small intestine): inhibits gastric and pepsin
secretion & Stimulates pancreatic and intestinal secretion.
Digestive Enzymes
- They are secreted by: Salivary glands and tongue.
Stomach pancreas.
- They break molecular bonds in large organic molecules (carbohydrates,
protein, fat) in a process called hydrolysis.
I. Enzymes of salivary glands:
Ptyalin: a salivary alph-amylase.
- Acts on starch (maltose, maltotriose, glucose).
- Ptyalin continues to work in stomach as long as the bolus of the food remains
intact.
Lingual lipase: inhibits fat digestion.
Kallikrein: splits off vasodilating protein (such as bradykinin) from plasma.
II. Pancreatic enzymes:

Enterokinase: a brush cell border enzyme which converts trypsinogen to
trypsin which converts the remaining proteolytic pro-enzymes to their active
forms.
Pancreatic amylase: hydrolyses most starch to disaccharides, trisaccharides.
Brush cell border disaccharidase: results in monosaccharides (glucose,
galactose and fructose), for example:
- Sucrase: breaks down sucrose to glucose and fructose.
- Lactase: converts lactose to glucose and galactose.
- Maltase: converts maltose to glucose.
- Isomaltase: converts isomaltose to maltose and glucose.
Pancreatic proteases: specific polypeptides split peptides into amino-acids.
Pancreatic lipases: digest fats to fatty acids.
Digestion and Absorption
(1) Carbohydrates digestion and absorption:

- starch digestion begins in the mouth via salivary amylase.
- pancreatic amylase hydrolyzes starch into tri- and di-saccharides.
- disaccharidase results in monosaccharides (glucose, galactose and fructose)
- Sucrase: breaks down sucrose to glucose and fructose.
- Lactase: converts lactose to glucose and galactose.
- Maltase: converts maltose to glucose.
- glucose and galactose are absorbed through a sodium-dependant co-
transporter increase in sodium facilitates absorption.
- fructose enters by glucose transporter 5, which does not requires sodium.
(2) Protein digestion and absorption:
- protein digestion is initiated in stomach by the action of pepsin.
- most protein digestion takes place in the intestine by the pancreatic protease.
- several polypeptidases convert polypeptides into peptides, which converted to
amino-acids by peptidases.
- free luminal amino-acids are absorbed via Na-dependent secondary active
transport.
- most amino-acids and peptides are absorbed in the jejunum.
(3) Fat digestion and absorption:
- Triglycerides are the most abundant lipids in the diet.
- digestion starts in the stomach (about 30% of fats are digested by lingual
lipase.
- most digestion and absorption occur in small intestine by pancreatic lipase,
which converts lipids into free fatty acids and 2-monoglycerides.
- the products of fat digestion are solubilized by incorporation into mixed
micelles (bile salts, monoglycerides, free fatty acids, phospholipids, cholesterol
and fat-soluble vitamins), which diffuse to the brush cell border of small
intestine, and the digested lipids are released from micelles to mucosal cells.
Liver Functions Tests

∙ Biochemical tests: Tests depending on bile pigments metabolism
Tests depending on bile salts
Transaminases
Tests depending on protein metabolism
∙ Hepatic imaging procedures
∙ Liver biopsy
---
I. Biochemical Tests:
(1) Tests depending on bile pigment metabolism:
a. Serum bilirubin: unconjugated, free, conjugated, Delta.
Normal levels: normal total serum bilirubin level is up to 1 mg.
unconjugated up to 0.8 mg _conjugated up to 0.2 mg.
b. Bilirubin in urine: cholebilirubin (conj.) appears in cholestasis, absent in hemolytic
anemia.
c. Urobilinogen in urine: increases in hemolytic anemia, absent in cholestasis.
d. Stercobilinogen in stools: increases in hemolysis, decreases in cholestasis.
(2) Tests depending on bile salts:
Bile salts appear in serum and urine in cases of cholestasis.
- Increase of serum level of bile salts results in pruritis and bradycardia.
- Bile salts in urine lead to frothy urine and positive hey sulphur test.
(3) Transaminases:
- Alanine aminotransferase (ALT) or serum glutamate-pyruvate transferase (SGPT).
- Aspartate aminotransferase (AST) or serum glutamate-oxaloacetate transferase
(SGOT).
ALT is liver specific, while AST presents in muscles, liver, heart and kidney.
ALT and AST leak into circulation in case of hepatocytes damage.
Measurement of transaminases activities is useful in:
- They are highly sensitive to acute hepatocellular injury: elevated activities may provide
an early clue to hepatic damage.
- Detection of anicteric liver diseases.
- Monitoring patients on hepatotoxic drugs.
- Follow up of chronic liver diseases courses and responses to treatment, but they are not
of prognostic value as falling values may indicate either recovery or deterioration
(extensive hepatocellular death).
(4) Tests depending on protein metabolism (hepatic synthetic function):
- Serum proteins: total serum protein is 6-8 g/dl Albumin: 3.5-5.5 g/dl
globulin: 1.5-3 g/dl
Albumin/Globulin (A/G) ratio is 2:1, which may be reduced or even reversed in chronic
liver diseases.
- Coagulation factors: prothrombin time and concentration evalute phase II coagulation,
which are of great prognostic value.
(5) Tests depending on fat metabolism:
1- Serum cholesterol is markedly increased in cholestasis and decreased in acute liver
disease.
2- Serum phospholipids levels: are increased in cholestasis.
(6) Tests to evaluate the biliary tracts:
- Serum alkaline phosphatase enzyme activity: the enzyme is derived from the biliary
epithelial cells, bone, kidney and intestinal cells.
- 5-nucleotidase and gamma-glutamyl transpeptidases, which have biliary origin, are
sensitive indicators of cholestasis or inflammation of biliary tract.
(7) Tests depending on detoxification:
- Bromosulphthalein: it is used for
diagnosis of Dubin-johnson and Roter diseases.
Differential diagnosis between haematemesis due to esophageal varices or peptic ulcer.
(8) Diseases-specific markers:
- Viral markers: in viral hepatitis.
- Metabolic markers: in Wilson's disease, haemochromatosis, alpha 1 antitrypsin
deficiency.
- Immunologic markers: in autoimmune hepatitis; ANA, anti-sms., gamma-globulin.
II. Hepatic Imaging Procedures:
- Plain x-ray. - Ultrasonography. - MRI.
- C.T scan: not used below 2 years because of small size of ?????
- Radionucleotide scanning: HIDA, PIPIDA, DISIDA.
- Cholangiography: percutaneous transhepatic in infants.
Endoscopic retrograde (ERCP) in children.
- Selective angiography.
III. Liver Biopsy.
****************************
Congenital Anomalies of GIT
The oral cavity:
∙ Cleft lip and cleft palate:
- cleft lip with or without cleft palate is 1:750 white births, cleft lip alone is 1:2500.
- more common in males.
- associated with congenital malformations and chromosomal abnormalities.
- cleft lip may vary from a small notch in the vemilion border to a complete separation
extending to the floor of the nose.
- It may be unilateral or bilateral.
- deformed, supernumerary or absent teeth are associated findings.
- Isolated cleft palate occurs in the midline and may involve only the uvula or may extend
to soft and hard palates.
∙ Palato-pharyngeal incompetence:
- Inability to perform an effective seal between oropharynx and nasopharynx during
swallowing or phonation.
The esophagus:
∙ Esophageal atresia and tracheo-esophageal fistula: the middle third of esophagus
failed to canalize and forms a blind upper end. There is a fistula between trachea and
lower portion of the esophagus.
N.B: the fetus with atresia can not swallow meconium leading to polyhydramnios.
∙ Achalasia: failure of relaxation of the lower esophageal sphincter due to absent
ganglia resulting in continuous contraction of the lower esophageal sphincter (LES). The
esophagus is dilated proximal to LES.
∙ Hiatal hernia: stomach herniates through hiatal opening.
∙ Pulsion diverticulum “Zenker's diverticulum”: congenital weakness of
cricopharyngeal muscles, so that food forces wall to bulge out in the upper end of the
esophagus.
∙ Webs and rings: webs (mucosal thickening), rings (muscularis thickening) resulting in
mild obstruction (abnormal esophageal contour).
∙ Esophageal stenosis.
∙ Laryngo-tracheo-esophageal cleft.
Stomach and Intestine:
∙ Congenital hypertrophic pyloric stenosis:
- It occurs more frequently in the first born male infants.
- more in infants with type B and O blood groups.
Pathology and pathophysiology:
pathophysiology diffuse hypertrophy and hyperplasia of stomach smooth
muscles in the wall of the antrum, so the antrum becomes thickened, elongated with
narrow lumen. The stomach musculature becomes uniformly hypertrophied in response
to outflow obstruction. Gastritis, bleeding, vomiting with subsequent loss of fluids and
electrolytes (H and Cl) resulting in dehydration and hypochloremic metabolic alkalosis.
∙ Congenital gastric outlet obstruction:
- results from pyloric atresia and antral webs.
- rupture of stomach may occur as early as first 12 hours of life.
∙ Gastric duplication:
- uncommon cystic or tubular structures that usually occur within the wall of stomach,
most of them are smaller than 12 cm and don't usually communicate with stomach lumen.
This leads to partial or complete outlet obstruction.
∙ Gastric volvulus:
- The stomach is attached to gastrohepatic, gastrosplenic, gastrocolic ligaments and to
the retroperitoneal tissues.
- Absence of one of these ligaments may allow stomach to rotate around itself resulting in
volvulus.
∙ Intestinal atresia, stenosis and malrotation:
- Atresia: complete obstruction of the bowl lumen.
- Stenosis: partial obstruction of the bowl lumen.
- Malrotation: incomplete rotation of intestine during fetal development.
∙ Duodenal atresia: ... polyhydramnios
- Failure of recanalization of the lumen in the forth to fifth weeks of gestation. An intact
membrane obstructing the lumen distal to ampulla of vater.
- Clinically presented by bilious vomiting, abdominal distension and jaundice.
- Double bubble sign: air in stomach and air in the proximal duodenum.
∙ Meckel's diverticulum:
- persistent omphalomesenteric duct with closed umblical end and atretic distal end of
the duct, leading to fibrous cord and Meckel's diverticulum.
- It is present in 2-3% of people.
- 3-6 cm length outpouching of ileum.
- 50-75 cm proximal to the ileocecal junction on the antimesenteric side of the intestine.
- attached to the umbilicus by a fibrous cord which contains cystic structures.
- The mucosal lining is the same as that of the adjacent ileum, but in 35% there is ectopic
gastric (acid secreting) or pancreatic (pepsin secreting) tissues near the tip.
- Complications: haemorrhage: occult to massive due to erosion of the mucosa of the
diverticulum with acid and pepsin.
Diverticulitis: pain and perforation with fecal peritonitis.
Intestinal obstruction: ileo-ileal intussusception or volvulus.
Littre's hernia: diverticulum contained in ..... hernia.
∙ Congenital aganglionic megacolon “Hirschsprung disease”:
- It results from an abscence of ganglionic cells in the bowl wall (absence of Meissner's
and Auerbach's plexus).
- Begins in the internal anal sphincter and extends proximally to involve a variable
length of gut.
- The aganglionic segment is limited to the rectosegmoid in 75% of cases. In 10%, the
entire colon lacks ganglion cells.
- Clinically presented with delayed passage of meconium, chronic constipation,
enterocolitis and signs of intestinal obstruction.
∙ Imperforate anus:
- Failure of terminal ileum to communicate.....anus is replaced by a small dimple.
Intestinal Obstruction
- It occurs in 1:1500 live births.
- It may be partial or complete, simple or strangulation.
- simple obstruction is associated with failure of progression of bowl flow of luminal
contents.
- strangulating obstruction is associated with impaired blood flow to the intestine in
addition to obstruction of the flow of luminal contents. If it is not promptly relieved, bowl
infarction and perforation enssue.
Causes:
1) Adhesions:
- The most common cause of small bowl obstruction.
- Adhesions from a previous surgery, endometriosis or radiation.
2) Duodenal atresia: see before.
3) Chron's disease: narrowing of the terminal ileum due to full thickness inflammation of
the bowl wall. Serosal adhesions from bowel to bowel also cause obstruction.
4) Gall stone ileus:
- occurs in elderly women with cholecystitis and cholelithiasis.
- Fistula develops between gall bladder and small bowel. Stones pass into small bowel
and lodges at ileocecal valve resulting in obstruction.
5) Hirschsprung disease: see before.
6) Indirect inguinal hernia: the second most common cause of small bowl obstruction, as
bowl becomes trapped in inguinal canal.
7) Intussusception: the terminal ileum invaginates into the cecum (the most common
cause of intestinal obstruction between 3rd month to 6th year)
- Site: ileo-cecal and less commonly ceco-colic.
- The upper portion of the bowl “the intessusceptum” invaginates into the lower portion
“the intussuscipiens, dragging its mesentry along with it into the enveloping loop with
subsequent constriction of the mesentry, obstruction of venous return and edema and
bleeding from the mucosa with bloody stools.
8) Meconium ileus: in cystic fibrosis, meconium lacks...
9) Volvulus: see before.
Inflammatory Bowel Disease (IBD)
Definition:
a chronic relapsing lesion of unknown origin.
Subtypes:
(1) Chron's disease: granulomatous (as T.B but not caseating) disease of the whole gut,
mostly enterocolitis.
(2) Ulcerative colitis: non-granulomatous disease localised to the colon.
Aetiology and Pathogenesis:
- Mucosal state is under the control of many factors:
a. Factors activating the immune system: as luminal microorganisms, dietary antigens,
endogenous inflammatory stimuli.
b. Host defence, possible aetiology includes:
1. Genetic predisposition.
2. Abnormal structure of intestinal mucosa.
3. Infectious cause.
4. Abnormal host immune reactivity, leakage or localized activation of the immune
response.
5. Inflammation: final pathway: early lesions with neutrophils, late lesions with
mononuclear cells (macrophages, small lymphocytes), loss of the surface epithelial
absorptive function and lastly crypts secretion, resulting in repeated intermittent bloody
diarrhea.
N.B: Negative stool culture in bloody diarrhea is highly suggestive of I.B.D.
I. Chron's Disease
It is a chronic granulomatous ulcero-constrictive disease with segmental intramural
fibrosis and thickening of the terminal ileum leading to terminal ileitis.
- discontinuous spread through the entire GIT.
- “Skip areas” segmental regional enterocolitis.
- active phase is associated with extra-intestinal manifestations as iritis, uveitis,
sacroileitis, migratory polyarteritis, various renal disease secondary to periureteric
fibrosis and rarely systemic amyloidosis.
N.B: It affects kidneys indirectly through retroperitoneal fibrosis.
∙ Epidemiology: females > males, white race > non-white.
- common in USA, Europe and rare in Asia and Africa.
- 1-3/100,000
- less frequent than ulcerative colitis.
nd rd th th
- it occurs at any age, with a peak at 2 to 3 decade and a minor peak at 6 and 7
decade.
∙ Gross pathology:
- 40%: with small intestine involvement only.
- 30%: small and large intestine.
- 30%: duodenum up to mouth, very rare in mouth, esophagus and anal canal.
- it is a descending disease, i.e: foreward direction.
∙ findings include:
- transmural inflammation and epithelial ulceration.
- non-caseating granuloma (40-60% of cases).
- ulceration and fissuring and formation of fistulae with granular dull serosa.
- thickened edematous inflammed fibrosed intestinal wall.
- hypertrophy of muscle layer, narrowed lumen with string radiologic sign, skip lesions.
- mucosal ulcer like cancer sore with progressive disease, where ulcers coalease into
long serpentine linear ulcer oriented along the bowel axis with “cubble stone
appearance”.
- narrow fissures between folds may penetrate up to serosa resulting in adhesions with
adjacent loops of bowl. Extension of fissures leads to fistula and sinus formation.
∙ Microscopic:
- Inflammed mucosa with crypt abscesses (more common in ulcerative colitis than in
Chron's).
- Ulceration.
- Chronic mucosal damage, architectural loss, atrophy, metaplasia (gastric metaplasis).
- Non-caseating granulomas.
- Marked thickened fibrosed muscle layers.
- Late dysplastic epithelial changes, with increase risk of cancer (more common with
UC).
∙ Clinical Features:
- variable dominant recurrent episodes of diarrhea.
- crampy abdominal pain.
- fever lasting days to weeks.
- some melena.
- most of patients remit spontaneously or after therapy followed by relapse.
- weight loss, malabsorption and extraintestinal manifestations.
- consequences includes: fistula formation to intestine, skin, urinary bladder, vagina, ..
etc.
Abdominal abscesses, peritonitis, intestinal strictures and obstruction.
Rarely, massive bleeding, toxic megacolon. Bleeding is rare due to fibrosis (endarteritis).
II. Ulcerative Colitis
It is a chronic relapsing ulcero-inflammatory disease of the colon limited to mucosa and

submucosa. It is the most common of the IBD.
It begins in the rectum, extends proximally in a continuous fashion and sometimes
involves the entire colon.
It may be manifested by systemic disorders.
- It is characterized by:
1. Absence of well formed granuloma. 2. No skip areas.
3. superficial ulcer with surprisingly little fibrosis. 4. No mural thickening.
5. Normal serosal surface. 6. Great risk of carcinoma.
∙ Epidemiology: more common than Chron's, 4-6 per 100,000.
no particular sex, occurs at any age with a peak at 20-25 years.
- 80% rectum and rectosegmoid with retrograde extension to have a pancolic lesion
(ascending disease).
∙ Features:
- severe mucosal inflammation, lost vascular pattern, hyperemia and edema,
pseudopolyps.
- friable easily broad based ulcers (pathognomonic).
- ulcers interconnection: funnel shaped covered with thick mucosal bridges.. thining of
muscles which may lead to perforation and periodic abscesses.
- shutdown of neuromuscular function resulting in toxic megacolon and lately causes
atrophic attenuated mucosa.
∙ Microscopic:
- diffuse predominantly mononuclear cells inflammation in the lamina propria.
- neutrophilic infiltration of the epithelial layer, with crypt abscess.
- ulcers may extends in submucosa with granulation and degeneration in remission
phase.
∙ Clinical features:
- relapsing and remitting disorder with attacks of bloody mucoid diarrhea of insidious
onset and abdominal cramps and pain, tenesmus and colicky lower abdomen.
- fever, weight loss, considerable blood loss, electrolytes imbalance, intercurrent
infections, migratory polyarthritis.
∙ Complications:
- inflammatory strictures, dysplasia and carcinoma, massive bleeding, toxic megacolon.

Comparison Ulcerative colitis Chron's disease

Epidemiology Young woman, white more than black
Extent Mucosal and submucosal transmural
Location Mainly rectum, doesn't involve other Terminal ileum 30%, ileum and
areas of GIT colon 50%, colon 20%, involves
other areas of GIT from mouth to
anus
Gross features Friable crumbly mucosa (pathognomonic), Skip areas, fissuring ulcers,
pseudopolyps, multiple ulcers thickening, fibrosis of bowel
wall
Extra-intestinal manifestations: aphthous ulcers, uveitis, thrombosis, arthritis, gall
stones,..
Microscopic Diffuse inflammation of mucosa and Granulomatous (sacroid-like)
may involve submucosa with ulcers pathognomonic transmural
and crypt abscesses inflammation, ulcers,..
Clinical findings Recurrent lt sided abdominal cramps Recurrent rt lower quadrant
with bloody diarrhea and mucus colicky pain with diarrhea
(blood is uncommon)
Radiography Lead pipe in long standing disease String sign in terminal ileum
Complications Toxic megacolon, primary sclerosing Fistula, obstruction, Ca
cholangitis, spondyloarthropathy, oxalate renal calculi,
adenocarcinoma malabsorption, macrocytic
anemia
Malabsorption Syndromes
They are conditions that cause insufficient assimilation of the ingested nutrients as a
result of either deficient digestion or absorption.
- They can be categorized into:
Generalized mucosal abnormalities with multiple nutrient malabsorption.
Specific nutrients malabsorption (CHO, fat, protein, or meniral
malabsorption).
Aetiology:
∙ Failure of digestion: enzyme deficiencies, pancreatic insufficiencies, bile salts defects.
∙ Failure of absorption: decrease absorptive surface: gut resection.
Mucosal disease: Whipple's disease.
Chron's disease, hypersensitivity.
∙ Protein losing enteropathy: due to infections as giardia.
Classification of malabsorption disorders based on the prominant nutrient deficiency:

I. Carbohydrates malabsorption:
- Lactose malabsorption (congenital lactase deficiency, hypolactasia, 2ry lactase
deficiency).
- Congenital galactose malabsorption.
- Congenital sucrase-isomaltase deficiency.
II. Fat malabsorption:
- Pancreatic exocrine insufficiency: cystic fibrosis, Shwachman-Diamond syndrome,
chronic pancreatitis, PEM, Pearson syndrome.
- Liver and biliary disorders: cholestatic liver diseases, bile acid malabsorption.
- Mucosal causes: Abeta- or hypobeta-lipoproteinemia, Anderson's disease.
Drug induced: sulfasalazine: folic acid malabsorption.
Cholestyramine: Ca and fat malabsorption.
Phenytoin: Ca malabsorption.
III. Aminoacids malabsorption:
- Lysinuric protein intolerance: defect in diphasic acid transport.
- Hartnup disease: defect in free natural amino-acids.
- Blue diaper syndrome: isolated tryptophan malabsorption.
- Oast-house urine disease: defect in methionine absorption.
- Lowe syndrome: lysine and agenine malabsorption.
IV. Mineral and Vitamins Malabsorption:
- Congenital chloride diarrhea.
- Congenital Na absorption defect.
- Acrodermatitis enteropathica: zinc malabsorption.
- Menke disease: copper malabsorption.
- Vitamin D dependent rickets.
- Folate malabsorption: congenital or secondary to coeliac disease.
- Vitamin B12 malabsorption: autoimmune pernicious anemia.
Decrease gastric acidity.
Terminal ileal disease as Chron's disease or resection.
IE of vitamin B12 metabolism and transport.
- Primary hypomagnesemia.

∙ Celiac disease:
disease
An autoimmune disease (antibodies against gliadin fraction in glutin) usually occurs in
infancy with incidence in females more than males, involving duodenum and jejunum
leading to flattened villi with hyperplastic glands and chronic inflammation.
∙ Whipple's disease:
disease
a male dominant disease, caused by tropheryma whippelii bacilli with blunting of villi
and macrophages in lamina propria obstruction lymphatics and reabsorption of
chylomicrons.
Enterocolitis
Causes: - IBD. - T.B. - Food induced. - Drug induced
- Neonatal enterocolitis. - Neutropenic enterocolitis. - Yersinia.
(1) Antibiotic associated enteroclitis: (pseudomembranous)

- Infection by an enterotoxins producing strains of clostridium defficile in the lumen of
distal bowl following an antibiotic therapy (ampicillin, acoxacillin, cephalosporins and
clindamycin)
- Antibiotic therapy may predispose to growth of C. defficile by suppressing other
microorganisms or it may stimulates the organism to produce toxins (A&B).
(2) Neonatal necrotizing enterocolitis: rare in Egypt.
NEC is a syndrome of acute intestinal necrosis of unknown aetiology.
- Pathogenesis: a triade of intestinal ischemia (injury), enteral nutrition (luminal
surface) and pathologic organisms (E.coli, C. Perfringens, staph. epidermides and
rotavirus).
- Features: site: the terminal ileum and ascending colon are the most frequently
involved.
Coagulative necrosis without exaggerated cellular infiltrate which is a
characteristic histologic finding.
Gas accumulation in submucosa.
Progression of necrosis up to perforation, sepsis and death.
(3) Food induced enterocolitis:
- A protracted vomiting and diarrhea begins between one week and 3 months e.g: cow
milk.
- Jejunal biopsy shows flattened villi, oedema and inflammatory cells.
(4) Neutropenic enterocolitis:
- Deficiency of neutrophils, which may be due to congenital cyclic neutropenia or
associated with cancer chemotherapy, predispose to neutropenic enterocolitis involving
ileum, cecum and proximal colon with mucosal ulceration, perforation and high
mortalitiy.
(5) Yersinia enterocolitis: caused by yersinia enterocolitica.
- Mucosal ulceration in the ileum and necrotic lesion in Peyer's patches.
Gastrointestinal Lymphoma
- It is the most common malignancy in GIT in children.

- About 30% of children with non-Hodgkin lymphoma present with abdominal mass.
- Predisposing factors:
AIDS, ataxia telangectasia, Wiskot-Aldrich syndrome, agammaglobulinemia, severe
combined immunodeficiency, bone marrow transplant, celiac disease.
- Site: stomach, distal ileum, cecum or appendix.
- may be presented with crampy abdominal pain, vomiting, distension and palpable
abdominal mass.
- Bowel lymphoma should be ruled out in children above 3 years of age presenting with
an acute intussusception.
Cystic Fibrosis (Mucoviscidosis or fibrocystic disease)
- It is an inherited multisystem disorder of children and adults, characterized by

obstruction and infection of airways and maldigestion with its consequences.
- Genetics: 1:2000 caucasian child, AR trait, mutation occurs on the long arm of
chromosome 7 CF gene (CF transmembrane regulator).
∙ Features: Abnormal viscid secretion of exocrine glands, throughout the body.
Impermeability of cell membrane to Cl: increases salt content of sweat, pancreatic,
respiratory and intestinal gland cells, and decrease of water content leading to increase
viscosity.
∙ Pathologic changes:
- Lungs: bronchial obstruction, collapse, recurrent infections, lung abscesses, fibrosis
and bronchiectasis.
- Intestine: meconium ileus.
- Liver: jaundice due to cystic liver and focal biliary cirrhosis.
- Vas: obstruction and infertility.
- Pancreas: decrease intestinal contents of pancreatic lipase resulting in steatorrhrea.
Chronic inflammatory atrophic acini. Ductal obstruction by viscid mucous.

Viral Hepatitis
- Specific aetiologies: hepatotrophic viruses (A, B, C, Delta and E hepatitis)
- Non-specific: yellow fever, CMV, herpes simplex and zoster.
(1) Hepatitis A:
- Incubation period: 2-6 weeks with an average of 30 days.
- RNA virus. - Feco-oral route. - Mild acute illness. - recovery in in few
weeks.
- Jaundice increases with age. - No chronic phase. - No carrier state.
∙ Complications: very rarely fulminant hepatitis, cholestatic hepatitis, relapse.
∙ Pathology: Inflammation of portal areas and parenchyma. Green coloring due to
leakage of bile. Apoptosis of liver cells (rounded liver cells).
Recovery occurs with no scarring because hepatocytes can generates to a limited extent.
∙ Lab.: acute: HAV IgM Late after: HAV IgG (immunity)
(2) Hepatitis B:
- Incubation period: 6 weeks to 6 months.
- DNA virus has: HBs Ag (surface): general marker for infection and anti-HBs Ag
indicates immunity.
HBc Ag (core): anti-HBc IgM (acute) IgG (chronic).
HBe Ag (envelop): active replication of the virus.
- Transmitted through blood, sexual and vertical transmission.
∙ Pathology: Acute and chronic. Acute phase may be mild, moderate or acute massive
necrosis
Acute phase: inflammation of portal areas and parenchyma, green color, apoptosis
recovery as before.
Chronic phase: greyish-pink hepatocytes (ground glass).
- Treatment: interferons, lamivudine.
(3) Hepatitis C:
- Single stranded RNA virus. - I.P: 2 weeks to 6 months.
- Transmitted through blood, injection, dialysis, dental care services, tooth brush, others.
∙ Pathology: acute and chronic
- Acute phase is mild to mederate, rarely acute massive necrosis. Acute phase shows
portal inflammation, bridging necrosis, bile duct injury.
(4) Delta Hepatitis:
- RNA virus use HBV as a helper and it is non-infectious in absence of HBV infection.
- Transmitted through blood and injection.

∙ Pathology: acute and chronic phases as HBV.
(5) Hepatitis E:
- Like hepatitis A.
➢ Clinicopathological manifestations of viral hepatitis:
(1) Acute viral hepatitis:
- Diffuse cellular ballooning, focal or centrizonal necrosis. Portal tracts with chronic
inflammation (lymphocytes and plasma cells).
- Sudden onset of fever, anorexia, vomiting, jaundice and tender liver.
- elevated liver enzymes, increased urine urobilinogen, specific serum viral tests.
(2) Fulminant viral hepatitis: in B,C and Delta only, rarely in A and E.
- Acute liver failure with high mortality rate.
- submassive liver cell necrosis.
(3) Cholestatic viral hepatitis:
- Severe intrahepatic cholestasis with deep jaundice.
- Bilirubin in urine and absent urobilin in urine and feces.
- Complete recovery is not frequent.
(4) Chronic hepatitis:
a. Chronic non-active carrier state (persistent)
- lasting more than 6 months. It may lead to hepatocellular carcinoma.
- occurs in immunocompromised patients, vertical transmission of the virus and Down
syndrome.
- Pathology: portal inflammation, free of active liver cell necrosis.
b. Chronic active viral hepatitis:
- chronic illness with elevated liver enzymes.
- episodes of acute exacerbation may be seen in HCV infection.
- End result is cirrhosis, liver cell failure and carcinoma.
- Pathology: portal inflammation, liver cell ballooning, focal necrosis, piece meal
necrosis and bridging necrosis. Lobular inflammation, hyperplasia, fibrosis and
cirrhosis.
c. Cirrhosis of the liver.
d. Hepatocellular carcinoma.
Haemoglobin Metabolism
(synthesis and catabolism of porphyrin and heme)
∙ Structure: MW= 6700
- Each Hb molecule consists of: globin molecule and 4 heme groups (tetramer).
- Heme part, the binding site for oxygen, consists of ferrous complex of protoporphyrin
IX arranged in 4 pyrole rings.
- Globin part: 2 pairs of polypeptide chains (alpha and beta), linked through histadine
residuals with one heme molecule.
- In both myoglobin and Hb, the iron of the heme group is the ferrous form. When iron
becomes in ferric form, they are called methaemoglobin and metmyoglobin.
∙ Porphyrin and heme synthesis:
1. Biosynthesis of alpha-amino laevulinic acid (ALA) from the precursor
succinyl CoA + glycine ALA synthetase > alpha-amino laevulinic acid X2 >>
porphobilinogen.
2. Formation of porphobilinogen (PGB): by condensation of 2 molecules of ALA.
3. Conversion of porphobilinogen to cyclic tetrapyrole porphyrin ring and heme.
- Heme, the end product of ALA porphyrin synthetase inhibits ALA synthetase.
- PGB >> uroporphyrinogen >> Copropophyrinogen >> protoporphyrinogen >>
protoporphyrin plus Fe+2 >> Heme.
∙ Catabolism of heme and porphyrin (Bilirubin metabolism):
1. Source of bilirubin: it is produced from the breakdown of heme-containing proteins.
75% from red cell Hb and 25% from the breakdown of heme protein, enzymes,
myoglobin.
- Catabolism of 1 gm Hb produce 34 gm bilirubin.
- Hb gives globin and heme and heme gives iron and protoporphyrin, which is oxidized
to biliverdin, which reduced to bilirubin and CO (excreted from lungs).
- The unconjugated bilirubin has low water solubility but it is fat soluble (neurotoxic).
2. Transport: unconjugated bilirubin (UCB) is bound to albumin for transport to liver.
UCB bound to albumin doesn't enter C.N.S (non-toxic).
3. Uptake: UCB, but not albumin, is bound to Y and Z protein in the liver to be delivered
to the smooth reticulum within liver cells for conjugation.
4. Conjugation:
- UCB (indirect) is converted to a water-soluble (direct) bilirubin.
UCB uridine diphosphate glucuronyl transferase >>bilirubin monoglucuronide >> bilirubin
diglucuronide (direct).
- CB is water-soluble excreted in urine, not fat soluble.
5. Excretion:
- CB is excreted by hepatocytes into the bile to intestine.
- Most of CB is reduced by intestinal enzymes to stercobilinogen to stercobilin which is
not reabsorbed and excreted in stool. Small amount of CB will be hydrolyzed by intestine
or milk beta-glucuronidase enzyme, present in neoborn gut, giving UCB which is
reabsorbed (enterohepatic circualation).
∙ Disorders of Heme synthesis:
- Hepatic porphyrias: acute intermittent porphyria.
Porphyria variegata.
Hereditary coprophyrin.
- Porphyria cutaneo tarda.
- Erythropoietic porphyria: congenital porphyria “Gunther's disease”.
∙ Disorders of Globin synthesis:
1. Haemoglobinopathies: abnormal polypeptide chains are produced.
- Sickle cell disease: HbS (substitution of valine for glutamic at 6th position of beta chain)
2. Thalassemias: polypeptide chains are normal in structure but are produced in
decreased amounts.
a. Beta thalassemia: decreased beta chain production with compensatory increase in
HbA2 and HbF.
b. Alpha thalassemia: decreased alpha chain production.
******************

Basics for the Egyptian Fellowship of Pediatrics Endocrinology
Endocrinology

Physiology
∙ Hypothalamic hormones
- Most hypothalamic hormones promote secretion of their respective pituitary hormones
except: somatostatin inhibits GH secretion
PIF inhibit prolactin secretion.
Hypothalamic hormones Anterior pituitary hormones
1. Thyrotropin releasing hormone .. stimulates secretion of .. TSH
2. Corticotrophin releasing hormone .. stimulates secretion of .. ACTH
3. Growth hormone releasing hormone .. stimulates secretion of .. GH
4. Somatostatin hormone .. inhibits secretion of .. GH
5. Prolactin inhibiting factor .. inhibits secretion of .. Prolactin
6. Gonadotrophin releasing hormone .. stimulates secretion of .. Gonadotrophic hormones LH and FSH
➢ Anterior pituitary hormones:
TSH, ACTH, GH, Prolactin and gonadotrophins
➢ Posterior pituitary hormones:
ADH and Oxytocin
Growth Hormone
∙ Physiological functions of GH:
1) Growth effects: it increases skeletal and linear growth.
- over secretion of GH in children: gigantism.
- over secretion of GH in adults: acromegaly.
- decrease in secretion of GH in childhood: dwarfism.
2) Metabolic effects:
- protein metabolism: anabolic.
- fat metabolism: lipolysis.
- glucose: decrease in uptake and utilization of glucose leading to elevation of blood glucose.
∙ Regulation of GH:
1. Plasma concentration: negative feedback mechanism.
5-20 yrs: 6 ng/ml. 20-40 yrs: 3 ng/ml. 40-70 yrs: 1 ng/ml.
2. Starvation. 3. Hypoglycemia or decrease fatty acids in blood.
4. Exercise. 5. Excitement. 6. Trauma.
∙ Growth hormone provocation tests:
1. Arginine (IV). 2. Clonidine. 3. Insulin (obsoleted). 4. Exercise. 5. Sleep.

Antidiuretic hormone (vasopressin)

- It is synthetized in the supra-optic nucleus of hypothalamus, but stored and released from the
posterior pituitary.
∙ Action:
Action increases water permeability of the renal collecting ducts, so that water is
reabsorbed and the urine output decreases. In case of over secretion, fluid retention and
hyponatremia are the result.
∙ Regulation:
Regulation it is controlled by hypovolemia and plasma osmolality.
Hypovolemia stimulate venous and arterial stretch receptors, which in turn stimulate CNS to
supress the chronic inhibition of ADH secretion and consequently restore the ECF volume.
Increase osmolality stimulates hypothalamic osmoreceptors and increases ADH secretion so
that ECF osmolality is kept very close to 300 mosm/L.
It is inhibited by ethanol ingestion and weighlessness.
∙ Deficiency:
Deficiency marked thirst and urination.
In severe ADH deficiency (diabetes insipidus, DI), the patient may urinate 20 L/day and drinks
20 L water to compensate for losses.
Oxytocin
- It is synthetized in the paraventricular nuclei of hypothalamus and stored in the posterior
pituitary.
∙ Action:
Action It causes uterine contraction at term and contraction of the myoepithelial cells of the
mammary gland leading to milk flow from the breast “let down”.
- It is released in response to suckling at the breast and emotional factors as hearing the infant
cry.
Prolactin
∙ Action:
Action
1. on the breast: stimulates its development and breast secretion.
2. on the sexual organs:
in female: permissive effect on LH >> ovulation and formation of the corpus luteum.
in male: increases the growth of the prostate glands and seminal vesicles and
testosterone synthesis.
∙ Regulation:
Regulation
1. Feedback mechanism through hypothalamic-pituitary-gonadal axis.
2. Milk injection reflex: suckling or tactile stimulation leads to
increase prolactin and cosequently milk production and increase oxytocin and milk flow.
➢ Role of hormones in breast feeding:
(1) Estrogen: development of breast duct system, breast stroma and breast fat deposition.
(increase in size of the breast).
(2) Progesterone: development of the glandular tissue and alveoli. (breast secretions)
(3) Prolactin: stimulates milk secretion into alveoli during pregnancy and nursing.
(4) Oxytocin: contraction of breast myoepithelial cells. (milk injection)
Thyroid Hormones
T4 (tetraiodothyronine), T3 (tri-iodothyronine)
∙ The daily requirement of iodine:
- infants: 300 µg/day. - children: 70-120 µg/day. - Adolescents: 150 µg/day.
∙ Iodine metabolism:
1. Iodide transport (trapping): oral iodide reaches blood and concentrated in the thyroid.
2. Iodide organification: Iodide is oxidized by peroxidase to iodine and tyrosine is added to
give Monoiodothyronine (MIT) and diiodothyronine (DIT).
3. Coupling: 2 molecules of DIT couple to give T4, or one MIT plus one DIT give T3.
4. Storage of thyroid hormones: T3 and T4 are bound to thyroglobulin in the lumen of thyroid
follicles until needed.
5. Deiodination: MIT and DIT deiodinase enzyme iodine, which is reused in T3 and T4 synthesis.
6. Release of hormones: T3 and T4 bound to thyroglobulin protease and peptidase release of hormones
into blood stream and bind with thyroid hormone binding protiens.
7. Deiodination of T4 to T3: (in the liver, kidney, other tissues)
It is catalyzed by 5-deiodinase enzyme.
8. Degradation of thyroid hormones: occurs in liver, kidney and other tissue. Iodine is released
in blood and reused.
∙ Effects of thyroid hormones:

1. Calorigenic action: increase O2 consumption of all cells (increase BMR).
2. Protein metabolism: small amount leads to positive nitrogen balance (protein synthesis).
In large doses, they lead to protein catabolism.
3. Carbohydrates metabolism: increase CHO absorption from the GIT.
4. Lipid metabolism: increase formation of LDL receptors and decrease plasma cholesterol
levels.
5. Bone marrow metabolism: decreases in absence of T3 and T4.
6. Vitamins metabolism: T3 and T4 are necessary for hepatic conversion of carotene to vit.A.
7. Skin: in hypothyroidism, myxedema occurs due to water retention.
8. C.N.S: marked effects on brain development in young age.
9. Muscles: muscle weaknes in hypo- and hyperthyroidism.
10. Bone: in hypothyroidism, bone growth is slow with delayed epiphyseal closure.
11. Heart: increase in number and affinity of ß-adrenergic receptors.
12. Physical growth: potentiate effects of GH on peripheral tissues.
13. Sexual maturation: in hypothyroidism, delayed sexual maturation until bone age reaches
12-13 years.
∙ Regulation of thyroid hormones secretion:
- Hypothalamic control, thyrotropin releasing hormone
- Ant. Pituitary control, TSH stimulates thyroid h. synthesis and secretion

- Plasma level of thyroid h. (feedback mechanism)
- Factors inhibiting thyroxine 5-deiodinase (fasting, malnutrition, acute illness and certain
drugs as propyl-thiouracil) decrease T3 production.
∙ Thyroid function tests:

(1) Non-specific: in hypothyroidism
- CVS: sleeping H.R decreases, ECG of low voltage.
- Metabolic state: decrease in glucose level, increase cholesterol, decrease vit.A and serum
alkaline phosphatase.
- B.M.R: reduced.
(2) Specific tests:
1. Serum total T4 level: normally 4-11 µg/dl.
2. Serum TSH level: after neonatal period Normal level is < 6 µU/ml.
- high level indicates thyroid gland failure.
- low in hypothyroidism or hypothalamic and pituitary failure.
3. Serum thyroglobulin: absent in congenital athyroidic infants.
Increased in Grave's disease and endemic goitre.
Marked increase indicates differentiated carcinoma of the thyroid gland.
4. Serum thyroxine-binding globulin.
5. In vivo radionucleotide studies: useful in detection of thyroid ectopic tissue.
Using I123 or Technetium: hypothyroid < 10% uptake, hyperthyroid > 50% uptake.
6. ECG and EEG: ECG low voltage P and T and decreased amplitude of QRS complexes.
EEG low voltage.
7. X-ray studies (bone x-ray)
- retarded bone age.
- absent distal femoral epiphyseal ossific center at birth is diagnostic for congenital
hypothyroidism.
- skull x-ray: macrocephaly, large fontanelle, wide sutures, interstructural bones (wormian
bone).
- chest x-ray: cardiomegaly or peicardial effusion may occur.
8. Serum GH level may be abnormally low in primary hypothyroidism.
9. Resin T3 uptake: measures free TBG, not bound to thyroid hormone.
10. Detection of the cause of defective hormone synthesis (in transport, organification,
coupling, deiodination, thyroglobin synthesis).
11. Detection of auto-antibodies: in auto-immune thyroid diseases.
12. Thyroid U/S studies: size, location, shape of the gland, nodules: solid or cystic.
13. Thyroid gland biopsy: in case of lymphocytic thyroiditis and to exclude carcinoma.
14. Thyroid functions in preterm babies: postnatal thyroid functions in preterm babies are
qualitatively similar, but quantitatively low compared to that of term infants.
Preterm neonates below 28 weeks may have problems resulting from the immaturity of
hypothalamic-pituitary-thyroid axis and loss of mat. Cont.. of thyroid hormones, leading to
temporary decrease in thyroid hormones and a need of temporary thyroid hormones
replacement.
Calcium Homeostasis
- Parathyroid hormones and vitamin D are the principle regulators of calcium homeostasis.
- Calcitonin and parathyroid hormones (PTH) related peptide appear to be important
primarily in the fetus.
∙ PTH secretion is stimulated by hypocalcemia leading to: GIT absorption of Ca.
Bone resorption.
Decrease renal excretion of Ca.
1. G.I.T: PTH secretion stimulates 1-α hydroxylase in kidney to produce 1,25(OH)2 D3,
which stimulates synthesis of Ca-binding protein in the intestinal mucosa resulting in
intestinal Ca and phosphorus absorption & bone dissolution and demineralization.
2. Bone: bone resorption (mobilization of Ca from bone).
3. Kindney: inhibition of renal excretion of Ca.
- The above 3 actions results in normocalcemia.
∙ PTH related peptide:
- It is critical for normal fetal development and normal skeletal maturation.
- It can activate PTH receptors in kidney for synthesis of vit. D and decrease Ca excretion; and
in bone for bone resorption.
∙ Vitamin D: it is supplied by dietary intake and activated 7-hydrocholesterol in skin by
ultraviolet rays.
- Activation of vit. D: hypocalcemia and hypophosphatemia stimulate secretion of PTH, which
consequently leads to activation of vit. D as mentioned before.
∙ Calcitonin: it is secreted by the para-follicular cells of thyroid gland.
- The main biological effect is inhibition of bone resorption by decrease number and activity of
bone resorbing osteoclasts (opposing the action of PTH and vit. D), but it doesn't affect serum
calcium level.
Suprarenal (Adrenal) Gland

- The adrenal gland is composed of 2 endocrine systems; cortical and medullary systems.
I. The adrenal cortex:
- It consists of 3 zones: Zona glomerulosa (aldosterone)
Zona fasciculata (cortisol and adrenal androgens)
Zona reticularis (adrenal androgens)
(1) Mineralocorticoids: Aldosterone.

- It is the most potent mineralocorticoid produced primarily by Z.glomerulosa.
∙ Regulation: Renin-Angiotensin system (RAS).
Serum K level.
ACTH.
A. Renin-Angiotensin system:
- Hyponatremia results in minimal hypovolemia and hypotension, reducing renal blood flow.
This stimulates the juxtaglomerular apparatus to secrete renin, which converts
angiotensinogen (produced by liver) to angiotensin I angiotensin converting enzyme in lung and other tissues
angiotensin II angiotensin III.
- Both angiotensin II and III directly stimulate adrenal gland to secrete aldosterone.
B. Hypekalemia: directly stimulates aldosterone secretion.
C. ACTH: minor role in normal individuals, but significant in anephric man (after
nephrectomy).
∙ Action of aldosterone: it controls Na reabsorption (and consequently water) in distal
convoluted tubules, maintaining electrolytes equilibrium. The end result is stabilization of
blood volume and blood pressure.
(2) Glucocorticoids:
- They are formed in zona fasciculata.
- The principle one is cortisol (compound F) or hydrocortisone.
∙ Regulation of secretion:
- ACTH: it is secreted by the anterior pituitary under control of hypothalamus, in bursts of
varying amplitude throughout day and night.
Diurnal rhythm of cortisol secretion: pulses occur every 30-120 minutes;
highest ones at about the time of waking 1 am, in late afternoon and evening.
lowest ones 1-2 hours after sleep begins.
- Negative feedback mechanism: increase in serum cortisol level inhibits secretion of CRH and
ACTH secretion.
∙ The metabolic effects of glucocorticoids:
1. Catabolic effect: glycolysis (hyperglycemia)
proteolysis
lipolysis (increase FFA levels).
2. Circulatory and renal effects:
- They have a permissive effect on the action of epinephrine and norepinephrine on both heart
and blood vessels.
- A marked decrease in glucocorticoids results in decrease of cardiac output and shock may
develop.
- While a marked increase leads to hypertension.
3. Growth: in case of excess
- linear growth and skeletal maturation through direct inhibitory effect on the epiphysis, and
through decrease in the level of GH and insulin-like growth factor I.
4. Immunologic effects:
- They diminish the inflammatory process through blockage of histamine and pro-inflammatory
cytokines.
- decrease cellular immunity: in high doses, they deplete monocytes, eosinophils and
lymphocytes, especially T-cells.
- inhibit chemotaxis, phagocytosis of PMNL, so they do not arrive at the site of inflammation.
5. Effects on skin: fibroblasts.. increase bruising and slow wound healing.. cutaneous atrophy..
thinning of skin and striae.
6. Effects on bone: inhibit osteoblasts activity leading to osteoporosis.
7. Effects on calcium homeostasis: the overall effect is to decrease calcium level to normal in
case of hypercalcemia.
8. CNS: they decrease certain types of CNS edema and used in treatment of increased I.C.P
- They increase appetite, cause insomnia, irritability and emotional instability.
(3) Adrenal androgens:

- They are formed mainly by the zona fasciculata.
- Dehydroepiandrosterone sulphate (DHEAS) is the most abundant adrenal androgen in the
circulation.
∙ Regulation:
1. ACTH: controlled by hypothalamic CRH.
2. Additional factors: decrease expression of 3ß-hydroxy steroid hydrogenase in zona
reticularis and possibly increase in 17,20 lyase activity.
∙ The physiologic effects of adrenal androgens:
1. Growth promoting effect: increase retention of nitrogen, potassium, phosphorus and
sulphate.
2. Androgenic effects: development of male sexual characteristics.
Development of axillary and pubic hair in female.
II. The Adrenal Medulla:

- The principle hormones in the adrenal medulla are:
catecholamines (dopamine, norepinephrine and epinephrine)
∙ The physiologic effects of norepinephrine:
- It increases peripheral vascular resistance. This leads to increase in both systolic and
diastolic pressure and mean arterial blood pressure with slight decrease in pulse rate.
∙ The physiologic effects of epinephrine (adrenaline):
- increases the systolic blood pressure, pulse rate, cardiac output and..
- decreases the diastolic blood pressure by decreasing the peripheral vascular resistance.
- Hyperglycemia and calorigenic effects are more than those of norepinephrine.
∙ Metabolites of catecholamines:
3-methoxy-4-hydroxy-mandilic acid (VMA), metanephrine and metaepinephrine.
- measurement of catecholamines and metanephrine in urine is used to detect functioning
tumors of adrenal medulla.
Intersex
(Disorders of sexual development)
A variety of conditions in which a person is born with a reproductive or sexual anatomy that
does not seem to fit the typical definition of male or female.
- Genetic sex: 46XX or 46XY
- Gonadal sex: presence of testes or ovaries.
- Phenotypic sex: primary and secondary sexual characteristics.
- Gender identity: a person self representation as male or female.
- Gender role: sex typical behavior (toy preference, aggression,..)
- Ambiguity: difficulty in determination of sex.
- Sex determination: is the differentiation of gonads into testes or ovaries.
- Sex differentiation: is the differentiation of external and internal genitalia to male or female.
N.B: sex determinants: are number of genes critical for appropriate male genital development:
- presence of SRY (sex determining region of the Y chromosomes) gene: testes
determining factor.
- SOXq gene…..
- DAX1….
➢ Classification of Intersex:
- Male undermasculinization (male pseudohermaphrodism), in which the karyotype is 46XY or
a variety.
- Female masculinization (female pseudohermaphrodism), 46XX.
- True hermaphroditism:
hermaphroditism very rare.. either 46XX or 46XY with both ovarian and testicular
tissues present.
(1) Disorders in which both X and Y chromosomes are present:
∙ Male undermasculinization:
- Androgen deficiency: pituitary hormone deficiency.
Biosynthetic testis defect.
Gonadal dysgenesis.
- Androgen resistance: complete and partial.
∙ Less severe disorders of penis, testicles and breast development:
- hypospadius - micropenis - cryptorchidism - gynecomastia
- Aneuploidy syndromes e.g: 47XXY, 47XXX
(2) Disorders in which only X chromosome(s) are present:
∙ Female masculinization:
- Congenital adrenal hyperplasia (CAH).
- Congenital anomalies affecting genitourinary and anorectal systems.
- 46XX male (presence of SRY on X chromosome).
- Rarities e.g: maternal drugs and androgen secreting tumors.
∙ Normal female genitalia with little or no verilization:
- Gonadal dysgenesis: turner, pure gonadal dysgenesis, biosynthetic defects.
- Aneuploidy syndromes: triple XXX (47 XXX).
➢ Diagnosis and management:

N.B: Phenotypes that should be considered ambiguous are:
- Hypospadius without palpable gonads.
- Hypospadius with only one palpable gonad.
- Hypospadius with bifid scrotum.
- Micropenis without palpable gonads.
- Bilaterally non-palpable testis at term.
- Clitoral hypertrophy.
- Vulva with a single orifice.
- Inguinal hernia containing a gonad in a girl.
∙ History:
obstetric h.: endocrine disturbances, abnormalities of antenatal ultrasound scan.
Family h.: unexplained neonatal death, genital anomalies, infertility in close relatives.
∙ Complete physical examination:
- dysmorphic features, hypospadius, urethral orifice, gonads.
∙ Genital examination:
- length and girth of phallus.
- stretched penile length: at full term, normal mean = 3.5 cm.
Micropenis < 1.9 cm (< 2 SD)
- phallus diameter = 1-1.5 cm. If < 1 cm, it is likely to be assigned as female.
- palpable gonads, position of urogenital orifices.
∙ Investigations:
- Pelvic ultrasound: Mullarian structures.
Location, site and echogenicity of gonads.
Size and echogenicity of the adrenals.
- FISH or PCR: for SRY (Barr bodies)
- Karyotype: can be obtained in three days.
- Plasma 17-OHP (in 3 days).
- Plasma and urine Na/K ratio.
- Other steroids.
An Approach to a neonate with ambiguous genitalia
1. Chromosomal sex: chromosomal analysis should be done on T-lymphocytes from a
hyparinized blood sample (result is available in 5 days).
2. Gonadal sex:
a. palpation of gonads in scrotum or inguinal canal:
- gonads containing testicular tissue are either normal testis or ovitestis, as gonads containing
ovaries only don't descend.
- so, the presence of gonads in such position exclude simple verilization of a female infant.
b. pelvic ultrasound examination: presence or absence of uterus
- presence of uterus and ovaries with absence of palpable gonads indicates virilized XX female
next step is to measures adrenal hormones to rule out congenital adrenal hyperplasia.
Maternal plasma level of testosterone to exclude masculinizing tumor
- absence of a uterus with or without palpable gonads indicates:
male pseudohermaphrodism with XY karyotype: needs measurement of
testosterone, gonadotrophin, AMH, DHA
Defect in .. hormones synthesis → low plasma testosterone and DHA → high gonadotrophin
→ gonadal biopsy.
Defect in androgen action → normal or elevated testosterone and normal response by HCG.
Puberty
- Puberty occurs when hypothalamus secretes GnRH → release of LH and FSH from pituitary
→ sex steroid production → secondary sexual characters.
➢ Physiology of Puberty:
∙ The pre-pubertal stage: between childhood and approximately 8-9 years of age, the
hypothalamic-pituitary-gonadal axis is dormant (inactive).
∙ The peri-pubertal stage: 1-3 years before the onset of puberty:
- FSH and LH levels are low but measurable. LH secretion occurs in a pulsatile manner
during sleep.
- Very small amounts of gonadal steroids are able to suppress the activity of the axis.
- Adrenarche: adrenal cortical androgens play a role in puberty.
∙ with the onset of puberty:
1. The hypothalamic gonadostat becomes less sensitive to suppressive effects of sex steroids on
gonadotrophin secretion.
2. LH and FSH levels increases in blood, acting synergistically to promote gonad changes.
3. The nocturnal LH pulses continue to increase in frequency and amplitude leading to
enlargement and maturation of gonads and secretion of sex hormones.
- During middle and late adolescence in girls: positive feedback mechanism develops, whereby
rising levels of estrogen leads to distinct increase of LH resulting in cyclicity, leutinization and
ovulation.
∙ It is clear that GnRH is the primarily, if not the only, hormone responsible for the onset and
progression of puberty; because pubertal development can be initiated in sexually immature
humans by pulsed administration of GnRH.
∙ The first sign of puberty:
- Girls: the breast bud (10-11 yrs). 6-12 months later,.. pubic hair.
Mean age of menarche is 12- .. in USA.
- Boys: growth of testicles and thinning of scrotum are the first to occur. This is followed by
pigmentation of scrotum and growth of …. → pubic hair → axillary hair.
∙ Factors affecting the age of onset of puberty:
1. Osseous maturation: the onset of puberty is closely related to osseous maturation than to
chronological age.
2. Genetic factors: familial.
3. Race: black girls are more advanced in development of 2ry sex characters than whites.
4. Environmental factors: climate.
5. Nutritional and general health: good nutrition and health lead to earlier pubertal changes.
6. Body weight and composition: athlete girls are delayed in puberty or menarche.
➢ Precocious Puberty:
The onset of secondary sexual characters before 9 yrs in boys and 8 yrs in girls.
- Gonadotrophin dependent (True): hypothalamic-pituitary-gonadal axis is activated → LH
and FSH gonadal enlargement and secondary sexual characters.
- Gonadotrophin independent (precocious pseudopuberty): hypothalamic-pituitary-gonadal
axis is not activated.
(1) True (Gonadotrophin dependent):
- idiopathic: constitutional, functional.
- organic brain lesions: hypothalamic hamartoma, brain tumors, head trauma.
- hypothyroidism: if prolonged untreated.
(2) Combined gonadotrophin dependent and gonadotrophin independent:
- treated congenital adrenal hyperplasia.
- McCune-Albright syndrome.. late.
- familial male precocious puberty.. late.
(3) Gonadotrophin independent (pseudopuberty):
∙ Female: - isosexual: ovarian tumors, McCune-Albright syndrome, feminizing tumors.
- heterosexual: CAH, adrenal and ovarian tumors, exogenous androgens.
∙ Male: - isosexual: CAH, adrenocortical tumors, Leydig cell tumor, HCG secreting tumor.
- heterosexual: feminizing adrenal tumors, exogenous androgens.
(4) Incomplete precocious puberty:
- Premature thelarche, menarche or adrenache.
Short Stature
∙ Def.: a height 2 SD below the mean height for chronological age.
- If below 3 SD, it is pathological short stature.
∙ Causes: NIDSCED
- Normal variant short stature (familial, constitutional growth delay).
- Intrauterine growth retardation.
- Dysmorphic syndromes.
- Skeletal dysplasia: disproportionate. pathological
- Chronic systemic diseases.
- Endocrine disorders.
- Dire social circumstances (psychological).
➢ Proportionate and disproportionate short stature:

upper and lower segments, arm span, height measurement
- Lower segment: symphesis pubis to the floor.
- Upper segment: total body height – lower segment.
- Arm span: the distance between tips of middle fingers when the arms are fully extended.
∙ The mean upper/lower ratio: 1.7 at birth 1.3 at 3 yrs 1 at 7 yrs.
∙ The arm span/height ratio: in the first 7 yrs, arm span is 3 cm less than height.
8-12 yrs, they are equal.
After the age of 14 yrs, arm span is 1 cm more in girls and 4 cm more in boys.
➢ Classification:
Normal variant Pathological
(proportionate) 80 % 20 %
Disproportionate Proportionate
- Familial Short trunk Short limbs Onset
- constitutional growth
delay Prenatal Postnatal
- skeletal - Achondroplasia
dysplasia - Rickets - Primordial (IUGR) - Endocrinal disturbances
- Inborn error of metabolism - Chronic systemic diseases
- Fanconi - osteogenesis - Chromosomal defects - psychosocial dwarfism
anemia imperfecta - Miscellaneous syndrome - chronic ……..e.g…...
1. Normal variants:
∙ Familial short stature: (small birth length, normal bone age, normal puberty time, short
adult height). Other possible factors: race, sex, size of parents and family members, nutrition,
emotional state.
- The child's projected adult height falls within 10 cm of average parental height percent.
- Normal growth hormone secretion.
∙ Constitutional growth delay: retarded bone age, delayed pubertal changes with normal
physical examination and history of delayed growth and sexual development.
2. Primordial:
a. I.U.G.R: B.W is 2 SD below the mean for gestational age.
b. Primordial dwarfism with premature aging: progeria and progeroid syndromes.
Short stature without associated congenital anomalies
- Silver-Russel syndrome: frontal bossing, small triangular face.
- Others: Bloom syndrome, Cornelia de lange syndrome.
3. In born error of metabolism:
∙ Storage diseases: mucopolysaccharidosis (MPS), mucolipidosis.
∙ A.A: aminoacidemia, aminoaciduria.
∙ Organic acids: organic acidemia and organic aciduria.
∙ Disorders of minerals metabolism: Wilson's disease.
4. Chromosomal defects:
∙ Autosomal: Down, Trisomy 18.
∙ Sex chromosomes: Turner syndrome.
5. Miscellaneous:
- Nonnan syndrome, cerebrohepatorenal syndrome, arthrogryposis.
6. Endocrine:
- Hypopituitarism, thyroid .., adrenal insufficiency, Cushing's, hyperaldosteronism, D.M, D.I.
7. Chronic systemic illness:
- Chronic infections including parasites, hepatic, renal, CVS, CNS,.. .
8. Psychological dwarfism (deprivation dwarfism):
- disturbed mother child relationship results in hypopituitarism (low IGF-1).
9. Skeletal dysplasia:
- defects in growth of tubular bone or spine: achondroplasia, metaphyseal …. .
- disorganized development of cartilage of skeleton: exostosis.
- abnormalities of cortical bone density: osteogenesis imperfecta, … , oste ….
➢ Clinical and laboratory evaluation:
(1) Medical history:
a. The child's birth length, weight and gestational age: in cases of familial and prenatal
pathological, birth length is near the 5th percentile for gestational age.
b. Prenatal history: infection during pregnancy , drugs (phenytoin, alcohol,..), .. .
c. Postnatal history: malnutrition, infection, infestation, GIT, CNS, pulmonary, ..
d. family history: height, weight and diseases.
(2) Physical examination:
a. differentiation between proportionate and disproportionate short stature. And then, separate
normal variants from proportionate pathological short stature.
b. manifestations of: chromosomal abnormalities and congenital anomalies.
c. developmental anomalies associated hypopituitarism as cleft palate, solitary max. cent.
incisor.
d. system by system examination.
(3) Laboratory data:
1. Bone age: normal in familial and skeletal dysplasia and retarded in almost all other causes.
2. CBC: anemia, infection, cancer.
3. ESR: increases in collagen-vascular diseases, chronic infections and IBD.
4. Urine analysis: pyelonephritis, GN, RT disease.
5. Stool examination: occult blood, parasites, ova.
6. Serum electrolytes and phosphorus: CAH, RT diseases, parathyroid disease, rickets,..
7. BUN and creatinine: occult renal insufficiency.
8. Serum albumin: malnutrition.
9. Serum ALT: hepatic diseases.
10. Karyotyping: it should be performed in all girls with short stature with or without clinical
features of Turner's syndrome.
11. Thyroid functions: hypothyroidism.
12. GH & IGF-1: hypopituitarism.
13. CT scan and MRI: in any case of short stature to exclude tumors, hypothalamic
hamartoblastoma and brain anomalies.
Obesity
2
∙ BMI = Wt in kg / (Ht ) in meters.
- overweight: BMI > 85th centiles.
- obese: BMI > 95th centiles.
- severely obese: BMI > 97th centiles.
∙ Obesity is caused by a disturbance n the energy balance equation with mismatch of energy
intake and expenditure.
- It can be caused by: excess dietary intake.
Reduced expenditure.
combination of both.
∙ Causes of obesity:
1) Functional: simple obesity due to excess dietary intake and lack of exercise.
2) Organic:
a. hypothalamic disturbance: pituitary tumors.
b. hypephagic syndrome: Pradar-Willi syndrome.
Lawrence-Moon-Biedle syndrome.
c. corticosteroids excess: Cushing syndrome; iatrogenic, pituitary, adrenal.
d. hypothyroidism: thyroid failure.
e. chromosomal: Down syndrome, Klinefelter syndrome.
f. cerebral diseases: tumors, infections, hydrocephalus.
∙ Complications of obesity:
- Increase in risk of DM, CVS diseases, cancer, respiratory diseases, asthma, sleep apnea,
infertility, degenerative joint diseases, proteinuria, anxiety and discrimination in both social
life and in the workplace.
- It shortens the life span.
∙ It is a chronic disease that requires a chronic therapy.
Complications of Diabetes Mellitus

I. Acute complications:
1. Coma: hypoglycemic, hyperglycemic, DKA, hyperosmolar non-ketotic comas.
2. Heart failure due to pulmonary edema.
3. Brain edema and convulsions.
4. Infections: specially UTI.
II. Chronic complications:

1. Diabetic foot.
2. Diabetic neuropathy.
3. Diabetic nephropathy.
4. Diabetic retinopathy.
5. Increased incidence of epilepsy.
6. Arteriosclerosis and hypertension.
7. Atrophy of subcutaneous fat due to repeated injections.

Basics for the Egyptian Fellowship of Pediatrics Respiratory
Respiratory

Embryology & congenital anomalies

Developmenet of the Respiratory System
I. Epithelium:
- derived from the endoderm of the foregut as the following:
1) In the 3rd week, a diverticulum called the laryngo-tracheal groove (the primordium of the
respiratory system) appears in the endodermal floor of the pharynx.
2) The edges of the groove unite together dividing the upper part of the foregut into two
parts: a dorsal part, the esophagus, and a ventral part, the laryngotracheal tube.
3) The upper part of the laryngotracheal tube form the larynx. The middle part gives the
trachea. And the lower part divides into 2 lateral outpocketing called lung buds.
4) The right lung bud is divided into 3 branches while the left lung buds is divided into 2
branches. Each bronchus is called the main bronchus.
5) Each bronchus branches and divides repeatedly up to about 17 subdivision forming the
bronchial tree of one lobe of the lung.
6) The terminal branches called the respiratory bronchioles and alveoli, which expands
only after birth.
II. Cartilage, muscles and connective tissue:
- developed from the subphrenic mesoderm.
Developmental Anomalies of the Larynx

Laryngomalacia Congenital subglottic stenosis
Vocal cord paralysis Congenital atresia of the larynx
Laryngeal webs Laryngocele and saccular cysts
Laryngo-tracheo-esophageal cleft
(1) Laryngeal atresia:

- It results from failure of recanalization of the larynx.
- It is incompatible with life.
(2) Laryngeal web (Incomplete atresia):
- It results from incomplete recanalization of the larynx.
- A membrane web forms at the level of vocal folds → partial obstruction of airway and
results in stridor, weak cry and respiratory distress.
(3) Laryngo-tracheo-esophageal cleft:
- The larynx and upper trachea may fail to separate completely from the esophagus,
extending to the level of the carina.
(4) Laryngomalacia:
- The most common laryngeal congenital anomaly and the most frequent cause of stridor in
infant and children.
- Congenital deformities or flabbiness of the epiglottis and supra-glottic area and weakness
of the airway walls → collapse of supraglottic structures inward during respiration.
- In about 33% of infants, associated additional anatomic finding may be present as
tracheomalacia, subglottic stenosis and vocal cord paralysis.
(5) Congenital subglottic stenosis:
- It is the second most common cause of stridor.
(6) Vocal cord paralysis:
- The third most common congenital anomaly causing of stridor.
(7) Congenital laryngocele and saccular cysts:
- Abnormal air-filled dilatation of the larynx communicating with laryngeal lumen.
(8) Posterior laryngeal cleft and laryngo-tracheo-esophageal cleft:
- Defect in the mindline of the posterior larynx..
 Tracheo-malacia (Major airway collapse, a newer name):

- It is a condition of the neonates and infants characterized by weakness of the supporting
tracheal cartilage and widening of the posterior membranous wall  tracheal collapse
specially during times of increased air flow (coughing, feeding, crying).
- Site: most commonly affects the distal third of trachea and can be associated with a
variety of congenital anomalies including C.V.S, developmental delay, GERD, T.E fistula.
- It is rarely present in combination with laryngomalacia because of the separate
developmental pathway.
- Types: Type 1: intrinsic tracheal abnormalities which can be associated with TEF.
Type 2: extrinsic anomalies (vascular ring) abnormal pressure on trachea.
Type 3: acquired due to prolonged intubation or chronic infection.
- Symptoms and signs: chronic or recurrent pulmonary infections, expiratory stridor and
coughing increasing with feeding.
N.B: Dying spells: episodes of progressive hypoxia, apnea, cyanosis, bradycardia and even
cardiac arrest which occur during feeding.
Congenital Anomalies of Lung

Pulmonary agenesis or aplasia pulmonary hypoplasia
Cystic adenomatoid malformation Pulmonary sequestration
Bronchogenic cysts Lung hernia
Congenital pulmonary lymphangectasia
Others: lobar emphysema and pulmonary cysts, bronchobiliary fistula.
 Lung Hypoplasia:
- Definition: a decrease in both number of alveoli (up to 67%) and number of airway
generation (up to 50%).
The entire pulmonary parenchyma and supporting structures and airways may be absent
below the level of carina.
- Cause: it is almost always secondary to another congenital anomalies (diaphragmatic
hernia, oligohydramnios, CVS; F4) and others.
- in infants with congenital diaphragmatic hernia, the lung is unable to develop normally
because it is compressed by the abnormally positioned abdominal viscera.
∙ Agenesis of the lung: absence of lungs due to failure of the respiratory bud to develop.
- Agenesis of one lung is more common than bilateral agenesis.
- Bilateral lung agenesis is incompatible with life. It is associated with: anencephally,
diaphragmatic hernias, urinary tract anomalies, thoracic dystrophy, oligohydramnios, right
sided heart malformations.
- Patients with unilateral agenesis or hypoplasia have few symptoms and non-specific
findings.
 Lung hernia:
- It is a protrusion of the lung beyond its normal thoracic boundaries.
- Causes: congenital (20%)
acquired following chest trauma or thoracic surgery or due to cystic fibrosis.
Congenital weakness of the lung of the supraplural membranes or musculature of the neck
may be a predisposing factors.
- Types: cervical hernia (>50%), all acquired hernias, neck mass increase with cough.
parasternal hernia: associated with rib anomalies.
paravertebral: paravertebral muscles usually prevents herniation.
- Prognosis: spontaneous resolution cay occur.
 Cystic adenomatoid malformation:
- It is the second most common congenital lung lesion (lobar emphysema is first).
- A single lobe of one lung is enlarged and often cystic, compressing the remainder of the
ipsilateral lung leading to its hypoplasia and frequently causing mediastinal shift with
compression of the controlateral lung.
- Histologic examination: little normal lung tissue and may be glandular elements, cysts are
very common but cartilage is rare.
 Bronchogenic cysts:
- They arises from abnormal budding of the tracheal diverticulum of the foregut, which is
lined with ciliated epithelium.
- Cysts become symptomatic when infected or enlarged to a degree causing pressure
symptoms.
 Pulmonary sequestration:
- A mass of non-functioning embryonic and cystic pulmonary tissue that receives its entire
blood supply from the systemic circulation.
∙ Intralobar sequestration: it is usually found in the lower lobe with no pleural covering.
∙ Extralobar sequestration: it almost always involves the left lung and is covered with
pleural cavity. It is strongly associated with diaphragmatic hernia.
 Congenital pulmonary lymphangectasia:
- It is characterized by greatly dilated lymphatic ducts throughout the lung.
- This abnormality present in three forms:
a. limited to lungs.
b. secondary to pulmonary venous obstruction.
c. a part of generalized disease involving other organs.
 Bronchobiliary fistula:
- It is a fistulous connection between the right middle lobe bronchus and the left hepatic
ductal system.
- Acquired lesions result from hepatic disease complicated by infection.
 Congenital lobar emphysema:
- A congenital deficiency of the bronchial cartilage, redundant bronchial mucosal flabs,
bronchial stenosis and external compression by aberrant vessels or a tumor leading to
overinflation of all 3 lobes of the right lung.
- Onset is usually during the neonatal period, but may be delayed up to 5th or 6th month.
- The condition affects the upper and the middle lobes.
- The emphysematous lung compresses the unaffected lung.
Physiology
Oxygen dissociation curve of Hb
∙ Definition: Hb sat.
2
PO
- It is the relationship between: Percentage saturation of Hb.
Partial pressure of oxygen in arterial blood (PO2)
∙ Hemoglobin curve:
- Oxygen binds Fe+2 in haem to form oxyhemoglobin.
- Sigmoidal shaped curve is due to positive cooperation, i.e: binding of one oxygen molecule
facilitates binding of the next, and similarly, the release of one molecule facilitates the
release of others.
- The effect of pH on oxygen binding of Hb is called Bohr effect:
 pH   affinity of Hb for O2 &  pH   affinity
-  PCO2, acidosis,  2,3-DPG (diphosphoglycerate),  temperature  shift of oxygen
dissociation curve to right (i.e: lower O2 saturation for a given PO2)
-  PO2, acute alkalosis,  2,3 DPG, hypothermia, Hb F  shift of oxygen dissociation
curve to left (i.e: oxygen affinity is increased, tissue hypoxia).
Pathology
Pathology of Bronchial Asthma
 Definition: it is a chronic inflammatory condition of lung airways resulting in episodic
airflow obstruction.
 Pathogenesis: It is an antigen-antibody reaction (type 1), with releasing of histamine that
causes:  capillary permeability  edema of bronchial submucosa.
Contraction of smooth muscles of bronchi.
In mucous secretion of bronchi.
- the end result is narrowing of bronchi.
 Pathology:
- Gross picture:
- Small bronchi are thickened and narrowed, and their lumen contain mucous plugs.
- Lungs are voluminous and pale due to emphysema.
- Microscopic picture:
- Small bronchi show: narrow lumen that contains mucus, sheded epith., and esinophils.
- Mucosa shows: hyaline thickening of the basement membrane.
hyperplasia of mucus glands.
- Submucosa shows: inflammatory edema
infiltration by esinophils and lymphocytes.
- Muscle layer shows hypertrophy.
 Complications:
- Chronic bronchitis.
- Emphysema  right sided heart failure.
Pathology of Pneumonia
 Definition:
patchy or diffuse inflammation of the lung.
 Staging:

∙ Traditional staging:
1- Stage of congestion: 1-2 days.
2- Stage of red hepatization: 2-4 days.
3- Stage of gray hepatization: 4-8 days.
4- Stage of resolution: 1-2 weeks.
∙ WHO (new) staging:
1- Stage of edema:  PO2, acidosis,  RR.
2- Stage of invasion with numerous phagocytic cells.
3- Stage of exudate: crepitation.
4- Stage of pus accumulation: chest indrawing.
5- Stage of toxemia.
6- Stage of irreversible toxemia.
 Pathogenesis:
1- Very early: congestion of the alveolar cells and accumulation of phagocytic cells 
alveolar wall thickening and partial impairment gas exchange process   O2,  CO2 
respiratory distress  fast breathing.
2- More accumulation of inflammatory exudate  alveolar sacs become full of exudate
after 2 days  crepitations.
3- Exudate changes into pus and fills the alveoli  decreases elasticity and less air in
alveoli  alveolar pressure < atmospheric pressure  the lower part of chest moves in
not out  chest indrawing.
4- After 2-3 days: X-ray shows tissue changes, consolidation, in the form of opacity.
 Pathology of lobar pneumonia:
- Aetiology is pneumococcal infection.
Stages Congestion Red hepatization Gray hepatization Resolution
Gross picture - enlarged, red, - enlarged, red, - enlarged, gray,
gray - fibrin is gradually
wet, spongy in consolidated. consolidated. liquified by proteolytic
Pathology consistency. - Cut section: dry. - Cut section: dry enzymes released from
affects - Cut section: - pleurisy. - pleurisy. the dead polymorphs.
a lobe frothy fluids. - enlarged hilar - enlarged hilar L.N. - phagocytosis by
L.N. macrophages.
- lymphatic drainage of
the liquified exudate.
- consequently, lungs
regain normal areation
Microscopic - Congested - Congested - alveolar congestion
alveolar capillaries. decreases.
capillaries - thickened - thin walls
- thickened alveolar wall. - spaces contain
alveolar walls. - alveolar spaces dead bacteria,
- alveolar contain bacteria, shrinked fibrin,
spaces contain fibrin,
fibrin erythrocytes, polymorphs,
bacteria and polymorphs. macrophages,
fluid exudate. hemolysed RBCs.
 Pathology of bronchopneumonia:
∙ Aetiology: staph., strept., pneumococci, H.influenza.
∙ Gross picture:
- Multiple consolidated yellowish patches, exudating pus on pressure. They may coallease
resulting in confluent bronchopneumonia.
- Fibrinous pleurisy and hilar L.N. enlargement.
∙ Microscopic:
- The walls of the affected bronchioles show congested capillaries, neutrophils and pus cells
- Adjacent alveoli show: inflammation, collapse, dilatation (compression emphysema).
 Causes of recurrent pneumonia:
pneumonia
 Genetic disorders: - cystic fibrosis. - sickle cell disease.
 Immune disorders/deficiencies: - Bruton agammaglobulinemia.
- IgG subclasses deficiencies.
- Severe combined immunodeficiency disease (SCID)
- AIDS.
 Leucocytes disorders: - Chronic granulomatous diseases.
- Hyper-IgE syndrome.
- Leucocyte adhesion defect.
 Ciliary disorders: immotile cilia syndrome, Kartagner's syndrome.
 Anatomical disorders: - sequestration. - bronchial cyst.
- lobar emphysema. - esophageal reflux.
- recurrent aspiration. - foreign body.
- TEF. - bronchiectasis.
Pleural Effusion
- Types: serofibrinous, empyema, hydrothorax, hemothorax, chylothorax.

- Exudates is characterized by: pH < 7.2 , specific gravity > 1015, protein level > 3 g/dL
lactate dehydrogenase > 200 with predominance of pAll.
- Causes: Bacterial pneumonia: the most common cause in children.
Heart failure, rheumatological causes, metastasis are the next common causes.
Other causes: T.B, lupus, uremia, pericarditis, rheumatoid arthritis.
Pathology of Neonatal Respiratory Distress Syndrome

- It is the cause of 30% of neonatal deaths.
 Pathogenesis:
- Normally, surfactant is synthesized and stored in type II alveolar cells, and then released
into alveoli, reducing surface tension and preventing collapse of alveoli at the end of
expiration.
- Mature levels of pulmonary surfactant are usually present after 35 weeks.
- Inadequate pulmonary surfactant  VQ mismatch (hypoxia and hypecapnia) & failure of
lung to develop a functional residual capacity with tendency of lungs to be atelectatic at
end-expiration because of high surface tension.
- Immature or injured type II alveolar cells (due to ischemia, hypothermia, hyperoxia,
hypotension, hypovolemia, prematurity)  decrease surfactant, which leads to
progressive atelectasia hypoventilation   
vicious circle
 PCO2,  PO2 and HCO3  hypotension and shock  
pulmonary vasoconstriction  alveolar hypoperfusion  impaired cellular metabolism.
 Pathology:
- Macroscopic: both lungs are symmetrically airless, collapsed and firm.
Lungs are deep purplish red and liver-like in consistency.
- Microscopic:
L/M: - extensive micro-atelectasia of alveoli and dilatation of interalveolar capillaries and
lymphatics.
- The alveoli and ducts are lined with acidophilic membrane (pink staining hyaline
membrane, composed of products of infant blood and destroyed alveolar cells). This
occurs in about 1 hour.
- Interstitial emphysema is and inconstant finding.
- After 36-72 hours after birth, epithelium starts to heal and surfactant synthesis takes
place.
E/M: - damaged and lost alveolar epithelial cells.
- swelling of capillary endothelial cells.
- disappearance of lamellar int...bodies.
 Complications:
- Air leak, PDA, bronchopulmonary dysplasia, anemia.
- Complications due to incubator procedures: as umbilical a. and v. catheterization,
intubation and hyperoxia.
Pharmacology and Treatment

Treatment of Bronchial Asthma
 Goals of therapy:
∙ Reducing impairments: - prevent chronic symptoms.
- maintain near normal lung functions.
- maintain normal activity.
∙ Reducing risks: - prevent recurrent exacerbation of asthma.
- provide optimal pharmachotherapy with no or minimal adverse effects.
 First line drugs for treatment of asthma:
I. ß2 -agonist: (Quick relief & Long-acting)
∙ Quick relief: prebuterol, turbutaline, albuterol, sulbotamol.
- Dose: 0.1-0.5 mg/kg/day in 3 divided doses.
- rapid onset of action, 5-30 minutes, and provide relief for 4-6 hours.
- for quick relief of bronchospasm in case of exacerbation.
- Side effects: tachycardia, hyperglycemia, hypokalemia, hypomagnesemia.
∙ Long-acting ß2 -agonists: formeterol, salmeterol.
- used with inhaled corticosteroids to control asthma and to prevent exacerbation.
- administered orally or by inhalation.
II. Corticosteroids:
- Inhaled corticosteroids (ICS) are the drugs of choice in patients with any degree of
persistent asthma.
- Severe persistent asthma may need oral prednisolone.
- Corticosteroids may be administered orally, by inhalation or through a spacer.
… degrees of asthma severity and their management:

Classification Step Daily Night PEF % Long term control Quick relief
symptoms symptoms
Mild 1  2 / week < 2 / month  80 % No daily medication Short acting
intermittent ß2 -agonist
Mild 2 > 2 / week but > 2 / month  80 % Low dose inhaled Short acting
persistent < 1 / day corticosteroid ß2 – agonist
Moderate 3 daily > 1 / week 60 – 80 Low dose inhaled Short acting
persistent % corticosteroids & long- ß2 -agonist
acting ß2-agonist

Severe 4 continuous frequent  60 % High dose inhaled Short acting
persistent corticosteroids & long- ß2 -agonist
acting ß2 -agonist or
LT inhibitors
III. Alternative drugs in between attacks:

1. Leukotriene antagonists:
∙ Zileuton: selective and specific inhibitor of 5-lipo-oxygenase.
prevents formation of both LTB4 and cysteinyl leukotrienes.
∙ Zafirlukast and Montelukast: selective reversible inhibitors of cysteinyl LT-1 receptors.
block effects of cysteinyl LTs.
- Side effects: elevated serum hepatic enzymes.
Esinophilic vasculitis.
Headache and dyspepsia.
2. Cromolyn and nedocromil:
- effective prophylactic anti-inflammatory agents.
- used as inhaler or aerosolized solution.
3. Anticholinergic drugs: inhaled ipratropium.
4. Theophylline:
- it is a bronchodilator that relieves airflow obstruction in chronic asthma and decreases its
symptoms.
- previously, it was the main stay of asthma therapy.
- Dose: 15-20 mg/kg/day in 3 divided doses.
5. Omalizumab:
- monoclonal antibodies that bind to human IgE preventing IgE from binding to their
receptors on mast cells and basophils.
- useful in moderate to severe asthma.
 To summarize asthma medications:

∙ Rescue medications:
medications Anticholinergic, atropine, & Adrenaline.
Fast-acting bronchodilator, albuterol as MDI, areolized or oral.
∙ Maintenance:
Maintenance non-steroidal, corticosteroid, leukotrienes modifiers, ...
- Non-steroidal: long-acting ß2 -agonists, salmeterol and formeterol.
- Corticosteroids: inhaler and oral.
- Leukotrienes modifiers: Singulair™ .
- Xolair™ (omalizumab): anti-IgE antibodies.
- Xanthines: theophylline.

Treatment of T.B
Antituberculous drugs and regimens
Corticosteroids Supportive care
I. Anti-tuberculous drugs:
(1) Isoniazide (INH): 10 mg/kg/day, oral or I.M. Bactericidal
∙ Indications:
Indications initial anti-tuberculous therapy.
∙ Metabolism:
Metabolism metabolized by acetylation in liver.
∙ Side effects:
effects - peripheral neuritis; due to competitive inhibition of pyridoxine utelization.
- C.N.S. toxicity; rare and with overdose.
- Hepatotoxicity; rare, in the form of jaundice, abdominal pain, vomiting,
increase in serum transaminases.
- Allergic manifestations; rare.
- Drug interaction; increase in phenytoin level up to toxicity.
- Rarely, pellagra, hemolytic anemia, ↓G6PD, lupus-like rashes and arthritis.
(2) Rifampin (RIF): 15 mg/kg/day, oral or I.V. Bactericidal
- used in treatment of T.B and prophylaxis against meningococci and H.influenza,
∙ Indication:
Indication initial anti-tuberculous therapy.
∙ Metabolism:
Metabolism it is excreted through the biliary tract.
∙ Side effects:
effects - GIT disturbance and hepatotoxicity, increased when combined with INH.
- Thrombocytopenia, orange discoloration of urine and tears.
- Drug interaction: decrease effects of oral contraceptive drugs and interacts
with quinidine, warfarin and cortico….
(3) Pyrazinamide (PZA): 20-40 mg/kg/day Bactericidal
∙ Indication:
Indication it may be used as initial anti-tuberculous therapy, oral.
∙ Side effects:
effects arthralgia, arthritis and rarely gout and hypersensitivity.
(4) Streptomycin (STM): 20-40 mg/kg/day
∙ Indication:
Indication treatment of drug resistant disease and life-threatening forms of T.B.,I.M, I.V.
th
∙ Side effects:
effects affection of the vestibular and auditory portions of the 8 cranial nerve.
and less frequently renal toxicity.
∙ Contraindication:
Contraindication pregnancy; as 30% of infant will suffer severe hearing loss.
(5) Ethambutol (EMB):
- 15 mg/kg/day Bacteriostatic; prevent emergence of resistance to drugs
- 25 mg/kg/day Bactericidal; for treatment of drug-resistant strains, oral once or twice.
∙ Side effects:
effects optic neuritis, red-green color blindness.
∙ Contraindication:
Contraindication young children; as visual field and acuity can not be examined.
(6) Ethionamide (ETH): 15-20 mg/kg/day, oral 2-3 divided doses bacteriostatic
∙ Indication: treatment of drug-resistant T.B, and useful in T.B meningitis.
∙ Side effects: GIT disturbance and significant hepatitis.
Other drugs:
- They are less commonly used for T.B treatment; as they are less effective and more toxic.
∙ Aminoglycosides (Kanamycin, Amikin):
Amikin) are used in cases of streptomycin-resistant T.B.
∙ Cycloserine: infrequently used in children.
∙ Ciprofloxacin and ofloxacin:
ofloxacin are contraindicated in children; as they causes destruction
of the growing cartilage. They may be used in multi-drug resistant T.B.
 Treatment Regimens:
(1) Treatment of pulmonary T.B.:
1. A 6 months regimen of INH and RIF, RIF supplemented in the first 2 months with PZA:
- Success rate approaches 100% with less than 2% adverse effects.
2. A fourth drug, STM, EMB or ETH is added to the initial regimen in the following
conditions: - community rate of INH resistance is > 5-10 %.
- adult source case is at increased risk for drug-resistant T.B.
3. A 9 months regimen of INH and RIF: highly successful.
(2) Treatment of extrapulmonary T.B.:
- The same as pulmonary T.B. except in bone and joint, disseminated and C.N.S. T.B., which
need 9-12 months treatment duration.
(3) Treatment of HIV-seropositive children with drug-susceptible T.B.:
- INH, RIF and PZA for 2 months, followed by INH and RIF for 7 months.
- A fourth drug, ETH or STM, is used for disseminated T.B.
(4) Treatment of drug-resistant T.B.:
- At least, 3 and usually 4 or 5 drugs should be administered initially.
II. Corticosteroids:
prednisolone 1-2 mg/kg/day for 4-6 weeks, then tapering, is used in case of:
- T.B. meningitis. - Endobrochial T.B.
- T.B. with pericardial or pleural effusions. - Miliary T.B.
III. Supportive Care:

- Follow up for response and side effects.
- Adequate nutrition.
*****

Basics for the Egyptian Fellowship of Pediatrics Neurology
Neurology

Embryology & Congenital Anomalies

∙ CNS arises from the neural tube which arises from the ectoderm as follows:
- It appears in the 3rd week as a thickening of the ectoderm known as the neural plate, which
will form the neural groove, which has 2 elevated edges called the neural folds.
- the neural folds fuse together transforming the neural groove into neural tube.
- the fusion is absent in the anterior and posterior ends forming the anterior and posterior
neuropores, which are closed on days 23 and 25 consequently.
- the closed neural tube gives the spinal cord and the brain.
The Neural Crest
- It arises as a strip of ectodermal cells along the lateral edges of the neural groove.
- As the two edges fuse forming the neural tube, the 2 neural crests separate and migrate to
each side of the neural tube.
∙ Derivatives:
Derivatives each neural crest is segmented to masses which gives the following:
1. Sensory ganglia of the cranial nerves; 5,7,9,10.
2. Autonomic ganglia; both sympathetic and parasympathetic.
3. Dorsal root ganglia of all spinal nerves.
4. Neurilemma (Schwann) cells of peripheral nerves.
5. The medulla of suprarenal gland; chromaffin cells.
6. Melanoblasts of the skin, which produce melanin pigments.
7. Arachnoid and pia matter.
Development of the Spinal Cord
- The spinal cord is developed from the caudal part of the neural tube as follows:
1. At first, the neural tube is formed of one layer of simple columnar epithelium surrounding
an oval central canal.
2. Later on, this layer proliferates and the neural tube becomes formed of 2 thick lateral
walls and a thin ante of plate.
3. The lateral walls differentiate into 3 layers:
a. Inner ependymal layer; the cells of which gives rise to:
- the ependymal cells: lining the central canal of the spinal cord.
- the nerve cells (neuroblasts), which give migrate to the mantel layer.
b. Middle montel layer: it is formed of the nerve cells (neuroblasts) and neuroglial cells
which form the grey matter.
c. Outer marginal layer: formed of nerve fibers (ascending and descending tracts),
which will form the white matter.
4. A groove called sulcus limitans appears on the inner surface of the lateral wall on each
side dividing it into:
a. alar plate posteriorly, which contain sensory cells and forms the posterior horn of
the spinal cord.
b. basal plate anteriorly, which contains motor cells and forms the anterior horn of the
spinal cord.
5. Myelination of the nerve fibers of the spinal cord begins in the fourth month of
intrauterine life to the end of 1st year after delivery.
6. Development of the spinal meninges:
- dura matter: from mesoderm.
- arachnoid and pia matters: from the neural crest (ectodermal origin).
Congenital Anomalies of Spinal Cord

(1) Spina bifida occulta:
- Failure of fusion of the dorsal parts of one vertebrae around the spinal cord (which is
normal) mainly in the lumbosacral region.
(2) Meningocele:
- Failure of fusion of 2 or 3 vertebrae & the meninges bulges through the defect.
- Some neurological manifestations.
(3) Meningomyelocele:
- The spinal cord bulgs through the defect.
- Severe neurological manifestations.
(4) Myelocele:
- Failure of closure of neurological tube.
- The spinal cord is exposed though a defect in the vertebral canal;the most serious form.
Development of the Brain
∙ The brain develops from the cranial end of the neural tube as follows:
1. The cranial end of the neural tube expands to form the brain swelling.
2. Two constrictions appear in the brain swelling dividing it into 3 vesicles:
a. forebrain. b. midbrain. c. hindbrain.
3. The vesicles differentiate as follows:
a) forebrain: gives two optic vesicles (the future eyes), then divides into:
- a median port called diencephalen.
- two lateral vesicles called telencephalen (the future cerebral hemispheres).
b) midbrain: remains undivided.
c) hindbrain gives rise to:
- metencephalen forms pons and cerebellum.
- myelencephalen forms medulla oblongata.
Development of the brain stem

∙ As the development of the spinal cord, the lateral walls of the brain stem are connected by
a thin roof plate and a thin floor plate. And it will have a ventral basal lamina (containing
motor nuclei) and a dorsal alar lamina (containing sensory nuclei).
∙ Each wall shows sulcus limitans which separate the alar lamina from the basal lamina;
which differentiate into columns of sensory and motor nuclei.
A. Columns of the basal lamina (3 motor):
1. Somatic efferent columns differentiate into:
- 3rd and 4th nuclei in midbrain.
- 6th nuclei in pons.
- 12th nuclei in medulla oblongata.
2. Special visceral efferent column differentiate into:
- 5th and 7th nerve motor nuclei in pons.
- 9th,10th,11th nuclei in medulla oblongata.
3. General visceral efferent columns differentiate into:
- Edenger-Westphal nucleus (oculomotor nerve) in midbrain.
- Superior salivary nucleus (facial nerve) in pons.
- Inferior salivary nucleus (glossopharyngeal nerve) in medulla.
- Dorsal nucleus of vagus in medulla.
Physiology & Pathophysiology

The Cerebrospinal Fluid (C.S.F)
∙ Definition: it is a clear fluid that occupies the subarachnoid spaces and the ventricular
system around and inside the brain.
∙ Secretion: it is formed by active secretion (not by passive infiltration) by the choroid
plexus in the ventricular system, mainly in left ventricle.
∙ Amount and constitution:
- rate of production in normal child is 20 ml/hr.
- the total C.S.F volume is 50 ml in infants and 150 in adults.
- normal C.S.F pressure is 90-180 mm of water and most variations is due to coughing and
internal congestion of J.V in neck.
∙ Circulation: it circulates from the choroid plexus through the interventricular foramina
(foramen of Monro) to the 3rd ventricle, and then through the mesencephalic duct (aquiduct
of Sylvius) into the 4th ventricle, where it exits through 2 lateral apertures (faramina of
Luschka) and one median aperture (foramen of Magindi).
- it then flows through the cerebromedullary cistern down the spinal cord and over the
cerebral hemispheres to dural sinuses and then to venous circulation.
- the C.S.F contains approximately 15-40 mg/dL of plasma proteins.
∙ Functions:
- It is an approximately isotonic solution, acting as a cushion or a buffer for the cortex,
providing also a basic mechanical and immunological protection to the brain inside the
skull.
1. Mechanical protection of the brain.
2. Distribution of neuroendocrine factors.
3. Prevention of brain ischemia ( amount of C.S.F in the limited space inside the skull 
 I.C.P  facilitate for blood perfusion).
Pathophysiology:
- When C.S.F pressure is elevated, cerebral blood flow may be constricted 
 intracranial blood flow  neuronal and glial vulnerabilities.
The venous and lymphatic systems is also important in this equation.
Diagnosis and Therapy:
- C.S.F can be tested for diagnosis of a variety of neurological diseases.
- It is usually obtained by a procedure called lumber puncture (L.P) in attempt to count the
cells in the fluid and to detect the levels of protein and glucose.
- These parameters alone may be extremely beneficial in diagnosis of subarachnoid hge and
C.N.S infections (meningitis).
- C.S.F culture examination: yield the microorganism that cause the infection.
- By detection of the oligoclonal bands, an ongoing inflammatory condition (as mutiple
sclerosis) can be recognized.
- ß2 transferrin assay: in C.S.F leakage.
- Lumber puncture can also be performed to measure the I.C.P which may be increased in
certain types as hydrocephalus.
- Lumber puncture is contraindicated in case of high I.C.P which may lead to brain
herniation.
Thermoregulation
- Fetal thermogenesis is normally inactive.
- The fetus maintain a temperature approximately 0.5º C above maternal temperature.
- Heat production, immediately after birth is reliant on lypolysis of brown adipose tissue.
- Cold air and oxygen stimulate the sympathetic nervous system to increase epinephrine
which acts on the brown adipocytes to activate adenylcyclase and increase cytoplasmic
adinosine monophosphate cAMP.
- Lipase activity increases with release of fatty acids, which are used by adipocytes to
produce heat.
∙ Body temperature is regulated by thermosensitive neurons, located in the preoptic or the
anterior hypothalamus, to a normal range (36-37ºC).
∙ These neurons responds to changes in blood temperature as well as to direct neuronal
connections with cold and warm receptors in skin and muscles.
∙ Thermoregulatory responses include:
- redirecting blood to or from cutaneous vascular beds.
- increased or decreased sweating.
- extracellular fluid volume regulation (via arginine vasopressin).
- behavioral responses such as seeking a warmer or cooler environmental temperature.
➢ Hypothermia:
∙ In hypothermia, hypothalamic thermostat controls body temperature by increasing heat
production (release of thyroxine, catecholamines, increase in muscle tone and shivering),
and decreasing heat loss (vasoconstriction and decreased sweating).
- causes of excessive heat loss (radiation, conduction, convection, evaporation) 
- hypoxia  shock, vasospasm and hypoglycemia)  the end result is apnea, bradycardia,
pulmonary hypertension and haemorrhage, I.V.H, HIE.
∙ Treatment:
- prophylactic.
- gradual reheating and treatment of complications.
➢ Hyperthermia:
- Causes are environmental, dehydration and infection.
- hyperthermia   BMR   O2 consumption   HR & RR.
∙ in hyperthermia, hypothalamic thermostat controls the body temperature by:
-  heat loss (vasodilatation of peripheral vessels & stimulation of sweating)
-  heat production.
➢ The hypothalamic thermoregulatory mechanisms is effective within limits,
and thermoregulatory failure occurs in severe cases.
CSF Circulation
‫صورة‬
Lateral Ventricle Lateral Ventricle Choroid plexus
Foramen of Monro
3rd Ventricle
Aquiduct of Sylvius
foramen of Lushka 4th Ventricle foramen of Lushka

to subarachnoid space
arachnoid villi in dural sinus to systemic circulation
Foramen of Magendi
Pathology & Diseases

Pathology of Poliomyelitis
It is caused by poliovirus (type 1,2 and 3), which is transmitted by feco-oral route and
nasopharyngeal route.
∙ Neuropathy of poliomyelitis is caused by direct cellular destruction.
∙ Secondary damage may be due to immunologic mechanisms.
∙ The neuronal lesions occur in:
- Spinal cord (A.H.Cs).
- Medulla (vestibular nuclei, cranial nerves nuclei and reticular formation).
- Cerebellum (nuclei in the roof and vermis only).
- Thalamus and hypothalamus.
- Pallidum.
- Cerebral cortex.
∙ Meninges shows: acute lymphocytic meningitis.
∙ Lower motor neurons (A.H.Cs) of spinal cord and medulla oblongata shows:
- intracellular inclusion bodies, inflammation, loss of nerve cells and gliosis (fibrinosin in
nerve cells.
- this is followed by demylination of the corresponding muscles.
- death may occur due to paralysis of respiratory muscles.
Causes of Mental Retardation (MR)

 Non-organic:
- idiopathic: it is usually mild.
 Organic:
1. Genetically determined causes:
a) Inborn error of metabolism:
- A.A: PKU, tyrosinemia (AR).
- Organic acids: isovuleric acidemia (AR).
- CHO: galactosemia, MPS (all are AR, except Hunter which is XLR).
- Lipid storage diseases (AR).
- Purines and pyrimidine, Lesch-Nyhan (XLR).
b) Chromosomal abnormalities:
- Autosomal: Down, other trisomies, other deletion syndromes.
- Sex chromosomes: fragile X.
c) Degenerative brain diseases:
- metachromatic leukodystrophy (AR).
d) Neurocutaneous syndromes:
- tuberous sclerosis (AD).
e) Neuromuscular diseases:
- Duschene dystrophy (XLR).
2. Acquired causes: (causes of CP)
- Prenatal, natal and postnatal.
- Congenital hypothyroidism.
- Lead poisoning.
Pathology of Brain Tumors in Childhood
- There are 2 major histological types:

1. Glial cell tumor, the most common.
2. Tumors of neuroectodermal cell origin.
∙ Glial cell tumors:
1. Astrocytoma: consists of bipolar astrocytes.
2. Ependymoma: consists of polygonal cells arranged around blood vessels or empty
spaces.
3. Glioblastoma multiforms: marked cell axoplasia and cell necrosis.
∙ Neuroectodermal tumors:
- arise from primitive undifferentiated cell from embryonic remnants involving cerebellum,
cerebrum, pineal body and spinal cord, e.g:
- craniopharyngeoma: arises from Roshke pouch.
- dermoid epidermal tumor: from invagination of epithelial cells during closure of the
neural tube.
- chordoma: from the embryonic notocord.

 Treatment of Epilepsy:
1. Medical treatment. 2. Surgical treatment.
3. Ketogenic diet. 4. Psychotherapy.
 Antiepileptic Drugs:
∙ First line: - phenobarbital - phenytoin - valproate
- carbamazepine - benzodiazipines (clonazepam, diazepam)
∙ Second line:
- Lamotrigine (Lamictal)
- Topiramate (Topomax)
- Oxycarbamazepine (trileptal)
- Levetirocetam (keppra)
- Gabapentin (neurontin)
 Toxicity of Antiepileptic drugs:
1. Systemic toxicity:
- GIT upsets (dyspepsia, anorexia, nausea, diarrhea)
- elevated liver enzymes, leucopenia.
- gingival hyperplasia and weight gain (phenytoin).
- hair loss, hirsutism, coarse facies.
- osteoporosis, impotence.
2. Neurological toxicity:
- drowsiness, sedation, impaired cognition, insomnia.
- depression and mode changes, dizziness, vertigo.
- nystagmus, diplopia, ataxia, tremor.
- Dysarthria, headache, sensory, neuropathy.
3. Idiosyncratic reactions:
- rashes, exofoliative dermatitis, agranulocytosis, pancreatitis.
- Steven-Jonson syndrome, erythema,
- aplastic anemia, thrombocytopenia, hepatic failure.
 Withdrawal of Antiepileptic drugs:
- Barbiturates and Benzodiazepines: 10 % every 2 months.
- Valproate, phenytoin, carbamazipine, lamotrigine: 10 % every 1 month.
- In case of polydrug therapy: at least 3 months in between each others.

Basics for the Egyptian Fellowship of Pediatrics Metabolism
Metabolism & Metabolic diseases

Lipid Metabolism
∙ Main classes of lipids:

- Fatty acids:
acids saturated and unsaturated – essential and non-essential
essential fatty acids cannot be synthesized in the body: ………, linolenic and arachidonic
acids.
- Triglycerides (TG).
- Phospholipids:
Phospholipids sphingolipids (ceramide, cerebroside, gangliosides, sphingomyelin) &
phosphoglycerides.
- Cholesterol:
Cholesterol dietary & de no vo synthesis from acetate.
- Others:
Others carotene, vitamins A, D, E and K.
➢ Lipolysis
- Adipose tissue contains an enzyme hormone sensitive lipase (HSL) that hydrolyze TG.
HSL
TG  F.A & glycerol
++ --
Catecholamines, ACTH, Insulin (stimulate lipogenesis)
TSH, Glucagon
- F.A: - Bound to plasma protein, albumin or citrate (FFA)
- Non esterified  blood for oxidation  energy.
➢ Lipogenesis
- Synthesis of TG from FA, glycerophospate and non-fat materials (CHO).
- Site: liver, but also in adipose tissues.
➢ Metabolism of ketone bodies (acetoacetate, 3-hydroxybutyrate and acetone)
Ketogenesis Ketolysis Ketosis (ketonuria and ketonemia)

liver mitochondria mitochondria and extrahepatic tissues
∙ Ketogenesis:
- It occurs in liver mitochondria due to presence of 2 enzymes: (hydroxy-methyl-glutaryl)
HMG-CoA synthase and HMG-CoA lyase.
- They are formed in liver cells from active acetate (derived from oxidation of F.A and
ketogenic A.A)
Factors that  ketogenesis Factors that  ketogenesis
- Fasting and starvation - Feeding of glucose or CHO
- CHO deficiency - Insulin in case of D.M
- High fat low CHO diet
- Administration or hypersecretion of anti-
insulin hormone substances
- D.M due to impaired glucose oxidation
and increased F.A oxidation
∙ Ketosis:
- The main ketone bodies of blood are acetoacetate and 3-hydroxybutyrate.
- As the rate of ketogenesis , the rate of ketolysis  till reaches a maximum, after which
any  in ketogenesis leads to  in ketone bodies in blood.
- Ketosis is a condition characterized by elevated levels of ketone bodies in blood
(ketonemia) and their excretion in urine (ketonuria).
TG (in adipose tissue) lipase (lipolysis)  glycerol (gluconeogenesis in liver)  glucose

 F.A (ketogenesis in liver)  ketone bodies
ketonuria  urine
CO2, H2O, E.  acetyl Co A ketolysis Muscles
∙ Complication of ketosis:
- increase levels of acetoacetate and 3-hydroxybutyrate leads to acidosis and acidemia
which leads to coma up to death.
- electrolytes loss especially potassium.
Disorders of Lipoprotein Metabolism

∙ Hyperlipidemia:
Hyperlipidemia
6 inherited types [I, II a, II b, III, IV, V]
- All types, except type I, have an increased cholesterol level.
- All types, except type II, have an increased triglycerides level.
Disorders of Sphingolipids Metabolism
GM1 ganglioside ß galactosidase GM2 ganglioside Hexosaminidase gal-glc-ceramide ß galactosidase
Glc-ceramide glucosidase Ceramide ceramidase Sphingosine & F.A
pc ceramidesphingomyelinase ß galctosidase gal.ceramide Aryl sulphatase SO4 gal.ceramid

∙ Sphingolipidosis:
Sphingolipidosis
1. Tay-Sachs disease: (GM1 gangliosidosis I) in Jewish
- Defective enzyme is hexosaminidase A which converts GM1 to GM2.
- Clinical manifestations: it primarily affects CNS with no visceral involvement.
- Onset: about 5 months of age.. mental retardation
1st sign is increased startle response to low noise, then decreased eye contact and
hyperacuisis. Later on, progressive hypotonia, blindness and may be seizures.
- Fundus examination: cherry red spot on macula.
- Laboratory: decrease in serum hexosaminidase A activity.
2. Sandhoff disease: (GM2 gangliosidosis II) AR
- Deficiency of hexosaminidase A and B.
- clinical picture: similar to Tay-Sach plus hepatosplenomegaly.
3. Gauchers disease: AR in Jewish
- Defective enzyme is ß glucosidase  accumulation of glucocerebrosides mainly in RES
specially spleen and bone marrow.
- Clinically: MR, marked HSM, pancytopenia (bleeding, infections, pallor) due to
hypersplenism and bone marrow infiltration.
- 3 types: chronic adult (classic), infantile and juvenile.
- Lab.: CBC, X-ray distal femur (ERLenmyer flash shaped)
BM: Gaucher cells.
Enzyme assay in BM cells.
4. Niemann-pick disease: AR.
- Enzyme deficiency: Sphingomyelinase  accumulation of sphingomyelin in RES and
brain.
- Clinically: MR, HSM, early death.
- 3 types: A, B, C. Type B has no neurological manifestations.
- Investigations: Fundus: may be cherry red spots (as Tay-Sach)
BM: characteristic foam cells.
5. Metachromatic leucodystrophy: AR
- Enzyme deficiency: Aryl sulphatase A  accumulation of sulphated galactoceramide in
brain  white matter degradation.
- Clinically: MR, inability to walk, progressive hypotonia and hyporeflexia.
- Investigations: reduced enzyme activity in leukocytes.
6. Farber disease: AR
- Enzyme deficiency: ceramidase enzyme  lysosomal accumulation of ceramides
especially in joints.
- Clinically: presented in 1st year of life with
painful joints swelling and nodules on affected joint.
vocal cord nodules may occur resulting in stridor.
7. Krabble disease: AR
- Enzyme deficiency: ß- galactosidase enzyme  accumulation of galactosyl ceramide in
brain  white matter degradation.
- Clinically: presented around 3rd month of life with progressive severe MR, convulsions,
spasticity, opisthotonus and optic atrophy.
- Investigation: CT scan: white matter attenuation.
Enzyme assay in WBCs.

Carbohydrates Metabolism
∙ Dietary CHO:
- Polysaccharides: starch, amylose and amylopectin.
- Disaccharides: cellulose, sucrose, lactose and maltose.
- Monosaccharides: glucose and fructose.
∙ Complex CHO:
- Glycoproteins: proteins which have monosaccharides attached to it.
- Glycolipids: lipids and oligosaccharides.
- Proteoglycans: protein core, glycosaminoglycan and dermatan sulphate.
- Glycosaminoglycans: polysaccharides, hexosamine and uronic or galactose.
➢ Glycolysis
- Oxidation of glucose to pyruvate with generation of ATP in muscles, fat and non-
gluconeogenic tissues.
- It may occur in absence of oxygen (anaerobic), when pyruvate is converted to lactose.
- Glucose gives 2 molecules of ATP and NADH.
➢ Gluconeogenesis
∙ Synthesis of glucose from non-glucose precursors, especially amino-acids except (leucine
and lysine) and glycerol in liver, kidney or intestinal epithelium.
∙ Pentose phosphate pathway (Hexose monophosphate shunt):
- Site: cytoplasm of muscles, liver, fat cells, thyroid, erythrocytes and breast.
- consitsts of 2 branches: oxidative and non-oxidative.
- the net result is the production of:
12 NADPH, 6 CO2 and one glyceraldehyde-3-phosphate for each glucose-6-phosphate
molecule passing through the pathway:
Glucose  Glucose-6-phosphate  6 Hexophosphates   6 pentose phosphate  5 hexose phosphate
 
1. 12 NADPH, 6CO2, 12 NAPHI, 12H P
- Functions:
1. provides reducing equivalents e.g reduced NADPH for the reductive synthesis of
F.A, cholesterol and to maintain glutathione in reduced form inside erythrocytes
(G6PD) and (6 phosphogluconate dehydrogenase)
2. Source of ribose. 3. Oxidation of glucose into CO2.
4. maintain integrity of red cell membrane.
➢ Glycogenesis: the conversion of excess glucose to glycogen for storage.

➢ Glycogenlolysis: the conversion of glycogen to glucose.

Inborn Error of Metabolism

 Glycogen Storage Diseases:
- These are IEM leading to abnormal accumulation of glycogen.
∙ Type I: Von Gierk's (AR) hepatorenal
- Enzyme defect: Glucose-6-Phosphatase in liver and kidney.
- Clinically: marked hypoglycemia, marked hepaatomegaly, enlarged kidneys,
hyperlipidemia and stunted growth plus lactic acidosis
- Diagnosis: liver biopsy and liver enzyme assay.
- Treatment: frequent glucose feeds and restriction of fructose and galactose intake.
∙ Type II: Pompe's (XLR) no hypoglycemia
- Enzyme defect: lysosomal α-glucosidase.
- Clinically: normal at birth, manifestations develop within few months with triad of
marked hepatomegaly,
cardiomegaly and cardiomyopathy,
marked hypotonia (floppy infant).
∙ Type III: Cori's limit dextinosis. Enzyme defect: debranching 1,6 glucosidase
∙ Type IV: Anderson's. Enzyme defect: branching amylo 1,4 and 1,6 transglucosidase.
- The last 2 types are as Von Gierk's but mild.
∙ Type V: McArdle's no hypoglycemia
- Enzyme defect: muscle phosphorylase
- Clinically: presented in adult life with cramps on exercise, myoglobinuria, muscle
weakness and wasting.
N.B: Lactose ‫ سكر اللب‬glucose & galactose - - - Sucrose ‫ سكر الكل‬glucose & fructose
 Galactosemia: AR
∙ Enzyme defect:
defect galactose-1-phosphate uridyl transferase, which coverts galactose to
glucose, resulting in accumulation of galactose-1-phosphate uridyl with subsequent injury
to brain, liver and kidney.
∙ Clinically:
Clinically present at commencement of breast feeding with failure to thrive, vomiting,
diarrhea, jaundice and hypoglycemia.
Hepatomegaly, ascitis, cataract and mental retardation.
∙ Investigations:
Investigations Urine: galactose.
Blood: enzyme assay.
Neonatal screening.
∙ Treatment: lactose free milk.
 IEM of fructose:
1. Benign fructosuria:
- asymptomatic disorder due to deficiency of fructokinase enzyme leading to fructosemia
and fructosuria.
2. Fructose intolerance:
- Enzyme defect: fructose-1-phosphate adolase..accumulation of fructose-1-P inside
hepatocytes.
- Clinically: as galactosemia but after ingestion of sucrose (‫)سكر الكل‬.
nausea, vomiting, abdominal pain, hypoglycemia, growth retardation, hepatomegaly, liver
cell failure.
- Investigations: Fructosemia and fructosuria after ingestion of sucrose.
Liver enzyme analysis.
Disorders of Mucopolysaccarides Metabolism
- A group of inherited disorders caused by incomplete degradation and storage of

mucopolysaccharides (glycosaminoglycans), which are:
heparan sulphate, dermatan sulphate, keratan sulphate.
- All are AR except Hunter which is XLR.
1. Hurler syndrome: AR
- It is the severest form due to deficiency of α-L-iduronidase  dermatan and heparan
accumulation in tissue and excretion in urine.
∙ Clinically: - onset is after the first year of life
- progressive mental retardation and coarse facies.
- Macrocephaly and dolicocephaly.
- Thick lips, macroglossia, depressed nasal bridge and persistent nasal d..
- HSM, corneal cloudiness, deafness, progressive kyphosis, joint stiffness.
∙ Investigations:
- Plain X-ray: dysostosis mutiplex.
Spine: ovoid vertebrae, anterior peaking, spatulate ribs.
Upper extremities: claw hand, V-shaped deformity of radius and ulna.
- Lab.: dermatan and heparan sulphate in urine, tissues and amniotic fluid.
Enzyme assay in WBCs.
Presence of inclusion bodies (Alder-Reilly bodies) in WBCs.
2. Hunter: XLR
- As Hurler but there is no corneal cloudiness.
3. Other types: Shie (corneal cloudiness), Sanflippo (MR), Morquinos & Maroleux (no
mental retardation and no or slight corneal cloudiness).

Protein Metabolism
Essential Amino-acids (cannot be synthesized in the body) Non-essential amino-acids

Isoleucine, Leucine, Valine, Phenylalanine, Alanine, Aspartic acid, proline, hydroxyproline,
Tryptophan, Methionine, Arginine, Histidine, serine, glycine, glutamic acid, tyrosine, cysteine,
Lysine, threonine cystine, hydroxylysine.
∙ Essential Amino-acids:
Phenylalanine Tryptophan Histidine
Valine Isoleucine Arginine
Threonine Methionine Lysine
Leucine
Disorders of Amino-acids Metabolism
 Inborn Error of Metabolism

(1) Phenylketonuria: AR
∙ Enzyme defect: phenylalanine hydroxylase pathway.
- Accumulation of phenylalanine and its transamination metabolite phenylpyruvic acid
resulting in brain damage.
∙ Clinically: usually normal at birth.
- vomiting, progressive mental retardation (IQ < 20%).
- microcephaly, convulsions (1/3 of cases)
- blond with fair skin and blue eyes and eczema.
- neurologically: hypertonia and hyperreflexia.
∙ Investigations: raised phenylalanine in blood and phenylpyruvic acid in urine.
∙ Treatment: low phenylalanine diet (LofenalacTM Milk)
(2) Alkaptonuria: AR
∙ Enzyme defect: homogentisic acid oxidase, with accumulation of HGA.
- deposition of homogentisic acid in cartilage and other tissues.
∙ Clinically: ochranosis (black sclera and ear cartilage)
black diaper on exposure to air
osteoarthritis especially lumber spine.
(3) Albinism:
∙ Enzyme defect: tyrosinase pathway, defect in biosynthesis and distribution of melanin.
∙ Clinically: white hair, fair photosensitive skin.
Eyes: pale blue to light green, photophobia, nystagmus,  visual acuity.
∙ 3 Types: - Oculocutaneous: AR , the severest form.
- Ocular: X-linked.
- Cutaneous: AD , partial albinism.
(4) Homocystinuria: (1:160,000)
∙ Enzyme defect: cystathionine- synthetase (homocystine & serine = cystathionine)
∙ Clinically: - Normal at birth. Classically presented after 3 years.
- Progressive MR and failure to thrive, convulsions in 20% of cases.
- Marfinoid features: dislocateion of lens, but it is downward, arachnodactly,
high arched palate, lax ligaments, kyphoscoliosis.
∙ Investigations: elevated plasma methionine and urinary homocystine.
∙ Treatment: dietary restriction of methionine with cystine supplementation.
Vitamin B6 gives a dramatic response.
(5) Maple syrup urine disease: (1:175,000)
∙ Enzyme defect: branched chain ketoacid decarboxylase.
∙ Clinically: presented in the first week of life with
MR, areflexia and dysphagia, hypoglycemia, metabolic acidosis leading to coma.
Urine with a characteristic odor of maple syrup ‫خشب القيقب‬
∙ Investigations: leukocytes and fibroblasts enzyme assay.
∙ Treatment: decreased intake of branched chain amino-acids intake.
 Amino-acid Transport Defect
Generalized amino-acids transport defects (amino-aciduria):
- Overflow: A.A infusion, liver cell failure, IEM (phenylketonuria)
- Renal causes: Specific transport defects, e.g: cystinuria
General tubular damage, e.g: Fanconi syndrome.
∙ Specific transport defects:
defects
- Cystinuria:
Cystinuria defective transport of the basic amino-acids (cystine, ornithine, arginine and
lysine) in renal tubule and GIT.
- Hartnup's disease:
disease defective renal and gastrointestinal transport of neutral amino-acid
(tryptophan), resulting in malabsorption, ataxia, pellagra and rash.
∙ General tubular damage:
damage
1. Fanconi syndrome:
- Inherited: cystinosis, galactosemia, herd fructose intolerance, Wilson glycogen storage
disease type I (Von Gierk's).
- Acquired: Poisoning (mercury, lead, zink, arsenic)
Drugs: salicylate, cisplatinum.
Renal disease: ATN, NS.
Nutritional deficiency: vitamin B12, vitamin D and kwashiorkor.
- Laboratory: generalized amino-aciduria, glycosuria, hyperphosphatemia, rickets,
acidosis, hypokalemia, polyruria and hypouricemia.
2. Cystinosis:
- deposition of L-cystine crystals in renal tubules, RES and cornea.
- Clinically: as Fanconi plus RTA, progressive renal failure and HSM.

Disorders of Collagen Metabolism

∙ Collagen:
Collagen
- It is formed by: fibroblasts in connective tissues, osteoblasts in bone, chondroblasts in
cartilage.
 Disorders of Collagen Metabolism:
1. Scurvy.
2. Ehlers-Danlos syndrome type VI: a defect in lysyl hydroxylase.
- Musculoskeletal deformities, specially hypermobility of joints and poor wound healing.
3. Ehlers-Danlos syndrome type VIII:
- No proteolytic cleavage of the N-terminal peptide on procollagen.
- Clinically: hyperelastic skin and bilateral hip dislocation.
Purines and Pyrimidines
Purines: adenine, guanine, hypoxanthines and xanthines.

Pyrimidines: cytosine, uracil and thymidine.
 Disorders of Purines and Pyrimidines Metabolism :
∙ Causes of hyperuricemia:
1. Increased purine synthesis:
- Primary gout (25% of cases are due to increase de no vo synthesis)
- Lesch-Nyhan syndrome, type 1 glycogen storage disease.
2. Increased purine turnover:
- High purine diet, polycythemia, myeloproliferative and lymphoproliferative diesease.
3. Decreased excretion of uric acid:
- Primary gout (75% of cases), renal failure,
increased level of organic acids, e.g: exercise, alcohol, DKA, starvation,
hyperparathyroidism and lead poisoning.
4. Drugs:
- Thiazide and loop diuretics, pyrizinamide, salicylate in low doses, alcohol.

Tables Summarizing Metabolic Disorders

Disorders of Lipids, Sphingolipids
Disease Enzyme deficiency Substrate accumulation N.B.
Tay-Sach disease Hixosaminidase A GM1 CNS only,cherry red spots
Sandoff disease Hexosaminidase A&B GM2 CNS, HSM
Gaucher's disease ß-Glucosidase Glucocerbroside MR, HSM
Nieman-pick disease Sphingomyelinase Sphingomyeline MR,HSM,cherry red spots
Metachromatic leucodystrophy Aryl sulphatase Salfatide galactoceramide White matter degradation
Farber disease Ceramidase Ceramide Joint affection
Krabble disease ß-Galactosidase ß-Galctosyl ceramide White matter degradation
Disorders of Mucopolysaccharides
Hurler syndrome| AR α L-iduronidase Dermatan and heparan MR, coarse features and
sulphate(glucoseaminoglycans) corneal cloudiness
Hunter syndrome| XLR As Hurler but there no corneal cloudiness
Shei | AR Corneal cloudiness
Sanfillippo | AR Mental retardation
Morquinos | AR No mental retardation & slight or no mental retardation
Maroleux | AR
Disorders of CHO metabolism

Disease Enzyme deficiency Substrate accumulation N.B
(1) Glycogen Storage Disease
Type I: Von Gierk's Glucose-6-phosphatase Marked hypoglycemia, hepatomegaly, enlarged kidney,
Hepatorenal stunted growth, lactic acidosis, hyperlipidemia
Type II: Pompe's Lysosomal α-glucosidase Normal glucose level, triad of: hepatomegaly,
Flobby infant (acid maltase) cardiomegaly and hypotonia
Type III: Cori's limit Debranching (1,6
dextrinosis glucosidase) As Von Gierk's but mild
Type IV: Anderson's Branching (trans-glucosidase)
Type V: McArdle's Muscle phosphorylase Normal glucose level, muscle cramps on exercise
(2) Galactosemia
Enzyme defect: Galactose-1-phosphate MR, jaundice, hypoglycemia,
Galactose-1-phosphate uridyl transferase uridyl hepatomegaly after ingestion
of milk
(3) IEM of frucose
Benign fructosuria Fructokinase Fructose

Fructose intolerance Fructose-1-phospate Fructose-1-phosphate As galactosemia but after
adolase ingestion of sucrose
Inborn error of protein (A.A) metabolism

Disease Enzyme defect Substrate accumulation N.B
Phenylketonuria Phenylalanine Phenylalanine Brain damage I.Q<20%
hydroxylase pathway microcephaly,convulsion,blon
d,hyper-tonia and -reflexia
Alkaptonuria Homogentasic acid Homogentasic acid Ochranosis
‫اللون السود‬ oxidase Black diaper
Albinism Tyrosinase pathway Decreased malanin Photophobia & white
(3 types) hair
Homocystinuria Cystathionine synthetase Methionine in plasma After 3 yrs: MR, FTT,
Homocystine in urine marfinoid features
Maple syrup urine Branched chain MR, hypoglycemia,
disease (MSUD) ketoacid decarboxylase metabolic acidosis up to
coma & odor of Maple
syrup
Aminoacids Transport Defects: see above
***

Basics for the Egyptian Fellowship of Pediatrics Acid-Base & Electrolytes
Acid-Base & Electrolytes

Disorders

Normal Electrolytes Levels

Cations ECF ICF Anions ECF ICF
Na 142 10 Chloride 104 5
K 4 145 Bicarbonate 25 10
Ca 2.5 0.001 Phosphate 1.1 100
Mg 1.0 40 Sulphate 0.5 20
Proteins 1.1 8
Hypernatremia
➢ Causes:
Normal extracellular Na : water ratio is 140 mmol/L.
Hypernatremia occurs when this ratio is greater than normal.
1. Sodium excess (increased total body sodium):
a- excess IV saline.
b- primary hyperaldosteronism steroid therapy, Cushing's, Conn's diseases.
2. Water depletion (low total body water):
a- decreased water intake e.g in coma and heat stroke.
b- extrarenal: fever, thyrotoxicosis, burns, diarrhea.
c- renal: osmotic diuresis, diabetes insipidus.
How is the cause of hypernatremia established ?
- Diarrhea. - obstructive uropathy.
- NaCl and NaHo3 administration. - primary hyperaldosteronism.
- Renal dysplasia. - central diabetes insipidus.
- improperly mixed formula in tube feeding. - nephrogenic diabetes insipidus.
∙ Clinical manifestations:
- signs of dehydration: thirst, dry tongue, sticky mucus membrane.
- hyperpnea, irritability, muscle weakness, high pitched cry.
- seizures, coma.
Hyponatremia
➢ Causes:
1. Water loading:
hyponatremia with sodium retention ( total body sodium and water):
a. Hypertonic hyponatremia;
- secondary hyperaldosteronism, e.g: CHF, liver cirrhosis, nephrotic syndrome.
-  GFR in acute and chronic renal failure.
b. Hypotonic hyponatremia;
hyponatremia without Na retention:
- acute water overload:  I.V fluids.
- psychogenic polydypsia.
- inappropriate ADH secretion: thiazide, carbamazepine, T.B, lung carcinoma.
2. Sodium depletion: ( total body Na)
a. renal loss (Na > 20 mmol/L):
mmol/L) osmotic diuresis due to DM, ketonuria, renal tuberculosis,
Addison's disease.
b. Extrarenal loss (urine Na < 20 mmol/L): sweating, burns, vomiting, diarrhea, paralytic
ileus and pancreatitis.
How is the cause of hyponatremia established ?
I. If the is hypovolemic:
Urine Na concentration < 20 mEq/L: consider extrarenal diseases:
- GIT problems: vomiting, diarrhea, fistula, gastrocystoplasty.
- Skin problems: cystic fibrosis, heat stroke.
- 3rd spacing: burns, effusion, ascitis, muscle trauma, pancreatitis.
Urine Na concentration > 20 mEq/L indicates renal losses:
- diuretic induced. - osmotic diuresis.
- salt losing nephritis. - bicarbonaturia (RTA, metabolic alkalosis).
- meniralocorticoids deficiency. - pseudohypoaldosteronism.
II. If the patient is euvolemic:
Urine Na concentration is usually > 20 mEq/L:
- consider excessive ADH.
III. If the patient is hypervolemic, evaluate Na level:
Urine Na concentration < 20 mEq/L
consider edema forming status:
- Nephritis. - Congestive HF. - Liver cirrhosis.
Urine Na concentration > 20 mEq/L
- consider acute or chronic renal failure.
∙ Clinical picture:
Symptoms usually do not occur until plasma level of Na < 120 mEq/L, but may occur at
higher concentration in case of rapid decrease.
- GIT: nausea, vomiting, anorexia.
- C.N.S: headache, irritability, disorientation up to seizures, coma and death.
∙ Treatment:
- in case of C.N.S symptoms, urgent treatment is indicated by:
hypertonic saline 3% (1ml/kg increases Na level by 1 mEq/L)
rate: 1 ml/kg over 10-20 minutes.
Elevation of Na level by only 5-10 mEq/L is usually sufficient to stop hyponatremic seizures.
- Asymptomatic: calculate total Na deficit = (desired – actual) x 0.8 x body wt
give ½ of the amount over 6-8 hours and the rest over the next 24 hours.
Hypokalemia (serum K < 3 mEq/L)
∙ Common causes of hypokalemia:

- Diuretics, laxative, diarrhea.
- Metabolic alkalosis, especially in patient with pyloric stenosis.
- Severe DKA, RTA type 1, II, and Fanconi syndrome.
- 1ry hyperaldosteronism, Cushing syndrome, steroid therapy.
∙ Clinical manifestations:
- muscle weakness, paralysis, which leads to hypoventilation and apnea.
- abdominal distension, constipation, paralytic ieleus.
- Cardiac arrhythmia, polyuria.
- ECG changes (MCQs): flat or absent T-wave and there may be U-wave.
∙ Treatment:
- treatment of the cause.
- K replacement oral or I.V(preferably oral) KCl 15% (1mg= 2 mEq)
0.5-1 mg/kg/dose given as infusion of 0.5 mEq/kg/hr for 1-2 hrs.
N.B: each 1ml of KCl is added to 100 ml of I.V fluids, as K is never given by a push or
bolus.
Hyperkalemia (serum K > 6 mEq/L)
- It is a life threatening condition, causing asystole or ventricular fibrillation.

changes K >7.5  peaked T wave.
- ECG changes:
> 8  wide QRS complex.
> 9  loss of P wave.
> 10 asystole and ventricular fibrillation.
∙ Causes:
- Acute renal failure, adrenal failure, acidosis.
- Excess intake, haemolysis, thrombocytosis, leukocytosis.
∙ Treatment:
- Ca gluconate (10%): 0.5 ml/kg slowly I.V.
- Nebulized salbutamol: promotes cellular intake of K.
- Sodium bicarbonate 5%: 2-4 ml/kg I.V slowly.
- Glucose and insulin infusion: 2.5 ml/kg/hr of 20% glucose followed by
0.05 unit insulin/kg/hr.
- Peritoneal dialysis.
- Treatment of the cause.
Hypocalcemia
(normal level= 8.5-10 mg/dl)
- 99 % of body calcium is located in the skeletal system.
∙ The main causes are:
- Nutritional: inadequate vitamin D or Ca intake.
- Renal insufficiency:
-  serum phosphorus due to  GFR and secondary hyperaldosteronism.
-  activity of renal -hydroxylase which converts 25(OH)D into 1,25(OH)2D,more active.
- Nephrotic syndrome:  serum albumin leads to  total Ca level.
- Hypoparathyroidism, pseudohypoparathyroidism.
∙ Manifestation of Hypocalcemia:
- Tetany and cramps of muscle of extremities.
- Trousseau sign: carpal spasms.
- Chvostek's sign: cheek twitches.
- ECG: prolonged QT interval.
- Seizures and mental clouding.
∙ Treatment:
- Ca gluconate 10% slow infusion (over 15 minutes) at a dose of 200 mg/kg (2cc/kg) and
may be repeated.
MCQs:
- Normal serum magnesium level is ….. (1.5-2.5 mg/dl)
- Normal serum phosphorus level is …. (2.5-4.5 mg/dl)
- Normal serum chloride level is … (96-106 mEq/L)
*****

Basics for the Egyptian Fellowship of Pediatrics Nutrition & Development
Nutrition & Development

Vitamins & Minerals (MCQs)
∙ 9 vitamins cannot be synthesized by the body and must be supplied by in diet:

Folic acid Ascorbic acid (C) Pyridoxine (B6)
Thiamin (B) Niacin Riboflavin
Biotin Pantathenic acid
Vitamin A (Retinol)
∙ Functions: 1. visual cycle. 2. growth.
3. reproduction (spermatogenesis) 4. maintenance of epithelial cells.
∙ Recommended dietary allowance (RDA):
- Male: 1000 retinol equivalent (RE).
- Female: 800 “ “ “
∙ Toxicity: dry pruritic skin - hepatomegaly and cirrhosis - increased ICP.
Folic Acid
∙ Folate deficiency results in:
- Nutritional anemia (megaloblastic).
- Fetal neural tube defects (in pregnant woman).
∙ Prophylaxis from NTO in pregnant woman: 0.4 mg/day.
Vitamin C (Ascorbic acid)

∙ Daily requirements: 35-60 mg.
∙ Functions:
1. reducing agent in many body reactions.
2. CC integrity and wound healing.
3. Iron absorption from GIT.
∙ Deficiency: scurvy.
Vitamin B6 (Pyridoxine)
∙ Deficiency: irritability, convulsions.
- It is used as prophylaxis in patients receiving INH.
Vitamin B12 (Cobalamine)

∙ Deficiency: pernicious anemia, dementia, spinal degeneration.
Vitamin B (Thiamine)
∙ Deficiency: - Beriberi
- Fatigue, irritability, insomnia.
- Anorexia, vomiting, constipation.
- Tachycardia, polyneuritis, convulsions.
Niacin (Nicotinic acid)

∙ Deficiency: (3D) Diarrhea, Dementia, Dermatitis.
Vitamin B2 (riboflavin)
∙ Deficiency: - Dermatitis, angular stomatitis
- Photophobia, blurred vision.
- Poor growth.
Vitamin E (-Tocopherol)
∙ Deficiency: haemolytic anemia.
Copper Deficiency
- Microcytic anemia. - Osteoporosis. - Neutropenia.
- Neurological symptoms. - Depigmentation of skin.
Protective Functions of Oligoconjugates

1. Oligosaccharides: protect against E.coli, strept. pneumoniae, cholera, H.influenza B.
2. Glycoproteins: .. cholera.
3. Mucin: .. E.coli.
4. Lactadherin: rota virus.
5. Gangliosides: receptor analogues for heat labile toxins of E.coli
6. Glucosaminoglycans: decreases binding of HIV receptors.
Nutritional Disorders (MCQs)
- The average length gain in the 1st year is 26 cm / year, then 11 cm / year.
- The average weight gain in the 1st year is 7 kg / year, then 2.5 kg / year.
∙ Gomez classification: (based on wt for age)
- > 90 %: normal
- 75 – 90 %: Grade I (mild malnutrition)
- 60 – 75 %: Grade II (moderate malnutrition)
- < 60 %: Grade III (severe malnutrition)
∙ Wellcome classification: (based on wt for age & presence or absence of edema)
Wt/Age Edema is present Edema is absent
60-80 % Kwashiorkor Undernourishment
< 60 % Marasmic Kwashiorkor Nutritional marasmus

∙ Waterlaw classification: (based on wt/age – wt/length – length/age)
Wasted Stunted Wasted and stunted
Wt/Age   
Wt/Length  N 
Lt/Age N  
WHO Classification Guidlines for Pediatric Undernutrition

Wt/Age Wt/Height Height/Age % IBW
Wasted Normal or low < 5th percentile Normal < 85-90 %
Stunted < 5th percentile Normal < 5th percentile Normal
Mild malnutrition Normal or low < 5th percentile Normal 81-90 %
Moderate “ “ “ Normal or low < 5th percentile Normal 70-80 %
Edematous Normal or low Normal (edema) Normal Normal
(kwashiorkor)
Marasmus Low < 5th percentile Normal or low < 70 %
(visible severe wasting)
➢ Clinical signs of Kwashiorkor:

1. Edema. 2. Growth failure. 3. Muscle wasting.
4. Fatty infiltration of the liver (hepatomegaly).
5. Mental changes:
- apathy, mood changes, sad look, derit smile, lack of interest to surroundings, anorexia.
- due to loss of thiamine, B6, B12, vitamin E, zinc, phenylalanine.
6. Hair changes: - spare, easy pickable due to loss of vitamin A.
- hypopigmented due to lack of tyrosine.
- loss of luster due to lack of zinc, sulphate.
- flag sign: alternate areas of hypopigmentation and normal coloration.
7. Skin Changes: flaky paint dermatitis, hypopigmented areas of skin alternating with
hyperpigmented areas (hypopigmentation is due to loss of tyrosine).
8. Anemia: - Normocytic normochromic: protein deficiency.
- Microcytic hypochromic: iron deficiency anemia.
- Macrocytic normochromic: vitamin B12 and folate deficiency.
 Ten-steps approach in case of severely malnourished child :

1. Treat and prevent hypoglycemia.
2. Treat and prevent hypothermia.
3. Treat and prevent dehydration.
4. Correct electrolytes imbalance.
5. Treat infections.
6. Correct vitamins and minerals deficiencies.
7. Start cautious feeding, then:
8. Rebuild wasted tissues.
9. Provide stimulation, play and loving care.
10. Prepare for follow up after hospital discharge.
Developmental Milestones
I. Gross Motor II. Fine Motor & Vision

newborn limbs are flexed, symmetrical posture 6th wk Follows face in midline
Follws moving objects, turning head
6-8th wks raise head to 45° on prone position 4th m Reaches out far toys
6th m Sits with round back 6th m Palmar grasp
8th m Sits with straight back 7th m Transfer toys from hand to hand
8th-9th m Crawls 10th m Mature pincer grip
10th m Walks around furnitures 16-18 m Makes marks with a cryon
12th m Walks unsteadily, broad gait 18th m Tower of 3 cubes
15th m Walks steadily alone 24th m Tower of 6 cubes, draw a line
18th m Runs stiffly, ascends stairs. 2½ yr Tower of eight cubes
24th m Runs well, descends stairs. 3rd yr Bridge from amoed and circle
36th m Ride a bicylce, alternate feet on stairs 4th yr Steps and cross drawing
4½ yr square
< 5 yr Triangle drawing
III. Hearing, Speech & Language IV. Social, Emotional & behavioral
Startle to loud noises 6th wk Smile responsively
th
2-4 m laugh 6-8th m Puts food in mouth
7th m Turns to soft sounds 10-12th Waves by b y
7-10th m Da Da & Ma Ma indiscriminately 12th m Drinks from a cup using both hands
12th m Another 2 or 3 words 18th m Holds spoon and gets foot to mouth
18th m 6-10 words, parts of body 18-24th Symbolic play
th
24 m Simple phrase 2 yrs By-by, pulls of some clothing
2½-3 yr Talks constantly 3 yrs Interactive play
*****

Basics for the Egyptian Fellowship of Pediatrics Breast Feeding
Breast Feeding

Composition (Types) of breast milk

(Colustrum - Transitional – Mature)
Colusturm
- Viscous, yellowish, alkaline.
- It is the earliest breast secretion.
- Its secretion starts during 3rd trimester till 5th day postpartum.
- Amount: 20-50 ml/day.
- High proteins and minerals.
- High fat-soluble vitamins (especially vitamin K, which prevent hemorrhagic diseases of
the neoborn)
- Low CHO (lactose), low fat (easily digested).
∙ Advantages:
a) for the baby:
1. highly nutritive due to high content of proteins and minerals.
2. highly protective due to high content of:
- neutrophils and macrophages (immune cells).
- IgA (surface Ig).
- establishment of bifidus factor: as it converts lactose into lactic acid which decreases
the pH, preventing growth of enteric bacteria.
- lactoferrin; iron binding protein (bacteriostatic agent for E.coli through competition
for iron).
3. GIT mucosal membrane maturation:
- contains epidermal growth factor, which leads to mucous membrane maturation.
- stimulates secretion of brush border enzymes: sucrase and lactase.
4. initiates intestinal motility (gastrocolic reflexes):
- passage of meconium.
- protects against neonatal jaundice.
b) for the mother:
- suckling promotes milk production.
- correct minor nipple deformities.
- early involution of birth canal.
- psychological satisfaction.
Transitional milk
- from 6th to 10th day up to 1st month.

- composition is midway between colostrum and mature milk,
- but phosphorus is higher than both (may be due to its importance in growth of brain cells).
- protein and ash gradually decrease and fat, CHO, most vitamins increase.
N.B: lactose is the main CHO in milk not the only one.
Mature (established) human milk
- after 1st month.

- amount: 500-900(2000) cc/24hrs.
∙ composition:
- protein: 0.9 (1.1gm%); low protein than cow milk.
N.B: if protein intake is > 5 gm%, dehydration and non-protein nitrogen retention (urea,
creat) ensue.
- CHO: 7 gm% - monosaccharides (glucose, galactose)
disaccharides: lactose, lactulose.
Oligosaccharides and complex carbohydrates.
- Fat: 2.02 – 5.3 gm.
(MCQs: the main variant of milk is… (fat). TG, cholesterol, phospholipids, fat soluble vitamins)
- Minerals: 0.2 gm%.
- Electrolytes, vitamins and hormones.
N.B: premature milk: contains increased amount of protein, sodium chloride, magnisium
and zinc; but a decreased amount of vitamin A. The composition of premature milk changes
to approach that of term milk after few weeks.
➢ Carbohydrates in human milk (7gm%)
∙ Lactose: synthesized in the mammary gland.

- it is the source of galactose, needed for myelin synthesis in the nervous system (I.Q).
- stimulates the growth of lactobacillus bifidus:
lactic acid   pH  inhibits E.coli growth and stimulates Ca and Mg absorption. Also,
the acidic stool decreases the incidence of napkin dermatitis.
∙ Oligosaccharides: ‫مغناطيس‬
- Anti-infective, as they contain receptors for microorganisms  block their binding to
mucous membrane   infections.
➢ Human milk nitrogen
 Protein nitrogen (75%): Casein 80% non-soluble - non-casein 20% (whey) soluble.
 Non-protein nitrogen (25%): uric acid, urea, creatinine (if   harmful to the body).
∙ Casein:  PO4,  protein,  sulphur A.A.
- it is combined with Ca forming Ca caseinate  soft curds.
- in cow's milk, it is large, hard curds  difficult in digestion  colic and fermentation.
∙ Non-casein protein (milk protein, whey protein):
- -Lactalbumin: dominant whey protein.
- ß-Lactoglobulin: responsible for sensitivity (very low). It absent unless the mother drinks
cows milk.
- Lactoferrin. - Lysozymes.
- Ig, enzymes, hormones. - Epidermal growth factor.
- A.A: (taurine is neurotransmitter) .. I.Q.
➢ Electrolytes in human milk (Na, K, Cl)
∙ Na: low  physiologic weight gain without hemodynamic …, as Na causes water

retention.
➢ Hormones in human milk
∙ Pituitary: T.S.H, prolactin. ∙ Calcitonin.

∙ Erythropoietin. ∙ Corticosteroids.
∙ PG E&F helps peristalsis.
➢ Anti-infective (protective) properties of breast milk
1. bifidus factor: antagonize enterobacter.
2. IgA, IgM.
3. B12 binding protein.
4. lymphocytes.
5. amylase  degradation of cell wall polysaccharides. It has antigonococcal effect.
6. specific antibacteria, antiviruses, anticholera, rota, polio.
7. anti-staph factor.
8. lactoferrin: iron binding  inhibits E.coli, candida growth by  availability of iron.
9. lactoperoxidases: kill strept. and enteric bacteria.
10. C3, C5 opsonization.
11. lysozymes: bacterial cell wall destruction.
12. interferon: inhibit intracellular viral replication and decreases O2 generation.
N.B: - the chief chemical stimulator of milk secretion of … (prolactin).
- best stimulus for milk secretion suckling.
➢ Growth factors in human milk

- Breast milk contains various biologically active factors called growth factors:
1) Aminoacid, taurine, which serves many functions in the newborn; as neurotransmission
and as growth factor. It is almost absent in bovine milk, so it is added to artificial milk.
2,3) Epidermal growth factor & insulin-like growth factor type 1:
- they stimulate growth and development of gastrointestinal tract.
- colostrum contains higher levels of theses growth factors than mature milk does.
4) Vascular endothelial growth factor:
- stimulates growth of blood vessels.
5) Colony stimulating growth factors:
These are involved in directing the division and differentiation of bone marrow stem cells
and the precursors of leucocytes:
- GM-CSF: myeloid growth. Development of neutrophils, esinophils, macrophages.
(Granulocytes-Macrophages).
- Granulocyte CSF: development and activation of neutrophils.
- Macrophages CSF: development and activation of monocytes/macrophages.
- Multipotential colony stimulating factor.
6) Erythropoietin.
7) Mammary derived growth factor 1: stimulates proliferation of normal and malignant
mammary epithelial cells.
8) Nerve growth factor: stimulates growth of sympathetic and certain sensory nerves.
9) α-transforming growth factor: stimulate epithelial development and neural cells
proliferation in injured brain.
Comparison between breast milk & cow milk
Human Milk Cow's Milk

1. Protein:
- Dietetic protein - whey:casein ratio is 80:20. - whey:casein ratio is 20:80
fine, thin, easily digestible. tough, thick, hardly digestible.
- Non-dietetic - lactoferrin, immunoglobulin, - 
protein. lysosymes, essential amino-acids
2. Fat - Small fat globules, diurnal variation, ✗
-  lipase and essential fatty acids ✗
-  volatile fatty acids. ✗
3. Carbohydrates - ß-lactose (no fermentation)  - fermentation and excess gases
lactic acid   Ca absorption, and vomiting.
bacteriostatic.
4. Minerals
- amount -  to avoid hyperosmolality and -  ..
renal failure.
- Ca/P - 2/1.. better absorption - 4/3.. less absorption (rickets)
- Na -  to decrease renal solute load -
- grm - sufficient for 4-6 months. -
5. Bacterial content - sterile - high, unless well boiled.
6. Calories - 67 .. - insufficient..

Advantages of Breast Feeding
1. For the infant: premixed, right temperature and concentration.

- provide the ideal nutrition for the infant during the first 4-6 months of life.
- life-saving in developing countries.
- reduces the risk of gastroenteritis, and in premature infants, reduces the risk of
necrotizing enterocolitis.
- improves the cognitive development (I.Q), as it contains polyunsaturated fatty acids.
- enhance mother-child relationship.
- reduces risk of IDDM, IBD, SIDS in later life.
2. For the mother:
- promotes close attachment between the mother and the baby.
- contraception: reduces birth rate in developing countries.
- possible reduction of premenopausal breast cancer.
- help involution of birth canal.
3. Scientific explanation of some of the properties of breast milk:
∙ Anti-infective properties:
- Humoral:
- secretory IgA: provides mucosal protection.
- bifidus factor: promotes growth of lactobacillus bifidus, which metabolize lactose
into lactic acid and acetic acid decreasing pH. This inhibits growth of
gastrointestinal pathogens.
- lysosymes: bacteriolytic enzymes.
- lactoferrin: inhibits growth of E.coli.
- interferon: antiviral agents.
- cellular:
- macrophages: phagocytic, synthesis of lysosymes, lactoferrin, C3, C4.
- lymphocytes: T-cells: transfer delayed hypersensitivity responses to infant.
B-cells: synthesis of IgA.
∙ Nutritional properties:
1- protein quality: more easily digested 80-90 whey casein ratio.
2- hypoallergenic: may reduces subsequent atopic diseases.
3- lipid quality: rich in oleic acid which improves fat digestibility and absorption.
4- breast milk Ca : P is 2:1 enhances lipase lipolysis, and prevents hypocalcemic tetany.
and improves Ca absorption.
5- low renal solute iron content: bioavailabiltiy (40-50 % absorption)
6- long-chain polyunsaturated fatty acids: structural lipids, important in retinal
development.
➢ Claimed disadvantages of breast feeding:

- unknown intake: volume of milk is not known.
- transmission of infection: increased risk of transmission of maternal CMV, HBV, HIV.
- breast mild jaundice: mild, self-limiting, unconjugated hyperbilirubinemia, continue
breast feeding.
- transmission of drugs: antimetabolites, chloramphenicol.
- nutrients inadequacy: breast feeding beyond 6 months without supplementation leads to
poor weight gain, rickets.
- low vitamin K and marginal contents of vitamins C, E, B ….: insufficient vitamin K to
prevent hemorrhagic diseases of the newborn and ...
- potential transmission of environment-contaminants: nicotine, alcohol, caffeine,..
- less flexible: other family members can not help in when taken apart.
- emotional upset: difficulties or lack of success can be upsetting.
Contraindications of breast feeding
I. Maternal diseases:
- HIV, CMV, herpes simplex virus if lesions are on the breast.
- Acute maternal disease if infant does not have disease (T.B, sepsis).
- Breast cancer.
- Substance abuse. - insanity. - severe epilepsy.
II. Maternal drugs:
∙ Absolute contraindications:
- Antineoplastics. - Radiopharmaceuticals.
- Ergot alkaloids. - Iodide/mercurials.
- Atropine, chloramphenicol, cyclosporin.
- Lithium, nicotine, alcohol.
∙ Relative contraindications:
- Neuroleptics, tranquilizers, sedatives.
- Metronidazole, tetracycline, sulfonamides.
- Steroids, estrogen containing contraceptives.
Use alternatives if possible or monitor the baby for side effects (jaundice).
N.B: - breast feeding is not contraindicated in mastitis.
- mothers with HBV infection are free to breastfed their babies after the neonate has
received the appropriate recommended vaccinations against HBV.
III. Infantile causes:
∙ Absolute (permanent causes):
- Inborn error of metabolism; e.g: galactosemia, PKU,..
∙ Temporary:
- Acute illness; e.g: pneumonia, septicemia,..
- Breast milk jaundice: stop for 48 hrs, then resume again.
- Correctable surgical conditions; e.g: cleft lip and palate.

Breast Feeding and mother medication
Breast feeding is contraindicated - Some anticholinergic drugs.

- Radioactive substances.
Continue breast feeding, side effects are - Psychiatric drugs.
possible, monitor baby for drowsiness - Anticonvulsants.
Use alternative drugs if possible, - Choramphenicol, tetracycline,
monitor baby for jaundice metronidazole, sulphonamides,
cotrimoxazole.
Use alternative drug, may decrease milk - Estrogen containing contraceptives.
supply - thiazide diuretics.
Safe in usual doses - Most commonly used drugs.
*****

Basics for the Egyptian Fellowship of Pediatrics
Miscellaneous

Chemotherapy & Antimicrobial Drugs

Antibiotics
Classification
I. According to mechanism of action:
1. Inhibition of cell wall synthesis:

- penicillin, cephalosporins, INH, vancomycin.
2. Affection of cell membrane permeability:
- nystatin, amphotericin.
3. Inhibition of protein synthesis:
- chloramphenicol, tetracyclines, erythromycin, clindamycin.
4. Induction of cell death:
- aminoglycosides.
5. Affection of nucleic acid (DNA) metabolism:
- Quinolones.
6. Nucleic acid analogues:
- acyclovir, gancyclovir.
II. According to spectrum:
1. Narrow spectrum:
- penicillin, aminoglycosides.
2. Broad spectrum:
- tetracyclins, chloramphenicol.
III. According to wither they kill or arrest growth:
1. Bacteriostatic:
- chloramphenicol, tetracyclines, clindamycin, sulphamethoxazide.
2. Bactericidal:
- aminoglycosides, ß-lactam, quinolones, vancomycin, metronidazole, rifampicin.
*****

➢ Cephalosporins (of ß-lactam antibiotics) should be revised

∙ bactericidal through inhibition of bacterial wall synthesis.
∙ Classification:
1. 1st generation:
generation - mainly gram positive and some gram negative as E.coli.
- They do not pass to C.S.F.
- Oral: cephalexin, cefadroxil, cephradine.
- I.M, IV: cephalothin, cefazolin, cephaparin.
2. 2nd generation: st
generation - as 1 generation plus H.influenza and neisseria.
- Oral: cefaclor, cefuroxime.
3. 3rd generation:
generation - mainly gram negative as H.influenza and pseudomonas.
- they can pass to C.S.F.
- Oral: cefixime, cefpodoxime.
- I.M, IV: cefoperazone, ceftriaxone, cefotaxime.
4. 4th generation: rd
generation as 3 generation but more resistant to ß-lactamase.
- Cefipime.
∙ Pharmakokinetics: they are excreted by renal tubules and glomeruli:
cefoperazone and ceftriaxone can be excreted by bile and feaces.
∙ Toxicity:
1. Allergy, cross allergy with penecillin.
2. Nephrotoxicity.
3. Thrombophlebitis after I.V injection, muscle pain after I.M injection, GIT upset after oral
administration.
4. Anti-vitamin K leading to hypoprothrombinemia (cefoperazone).

Antifungal Drugs
I. Polyne macrolide:
∙ Amphotericin B: 0.5-1 mg/kg/day I.V.
∙ Nystatin: 100,000 unit/dose every 6 hrs, not related to weight.
- they bind to membrane ergosterol altering the membrane integrity.
- amphotericin is used in serious systemic infections, but nystatin is oral infection.
- side effects of amphotericin: - nausea, vomiting, fever.
- Hypersensitivity, phlebitis at injection site.
- Nephrotoxicity, hypokalemia, normochromic anemia.
II. Imidazoles:
∙ Clotrimazole.
∙ Miconazole: - infants: 30 mg/dose oral every 6 hours.
- children: 60 mg/dose oral every 6 hours.
∙ Ketoconazole: (> 2 years) 3.3-6.6 mg/kg/day.
- they inhibit fungal lipid, ergosterol, synthesis in cell membrane.
- uses: candidiasis, dermatophytes, systemic mycosis (ketoconazole).
- side effects: miconazole: nausea, vomiting, reversible liver dysfunction.
ketoconazole: nausea, vomiting, hepatitis, rash, gynecomastia.
III. Triazoles: (FlIt)3
∙ Fluconazole:
Fl 3-6 mg/kg/dose every 24 hours oral or slow IV.
∙ Itraconazole:
It 3-5 mg/kg/dose, oral.
- they inhibit ergosterol synthesis.
- uses: fluconazole is used in candida species, cryptococcus neoformans.
Itraconazole is used in aspergillus, histoplasma.
- side effects: GI disturbances, rash, headache, liver damage (fluconazole).
IV. Other antifungal drugs:
∙ Griseofulvin: 10 mg/kg/day divided into 3 doses.
- interferes with nuclear acid synthesis.
- used in wide spread dermatophyte infection.
- side effects: porphyria in susceptible individuals, photosensitivity, hypersensitivity,
hepatitis, headache.
∙ Flucytosine: neonates: 80-160 mg/kg/day divided every 6 hours.
children and adults: 50-150 mg/kg/day every 6 hours.
- inhibits DNA synthesis.
- used as adjunct to amphotericin in cryptococcus meningitis.
- side effects:
effects bone marrow depression, accumulation in renal failure.
∙ Candins: inhibit cell wall synthesis through inhibition of glycan synthesis.
- used in treatment of candidiasis and aspirgillosis.
- side effects: elevated liver transaminases.
∙ Terbinafine: used in dermatophytes infection.
 Another classification:
I. Drugs for systemic mycotic infection:
a. affect ergosterol:
- pores formation in ergosterol: amphotericin B.
- inhibition of ergosterol synthesis: azoles: ketoconazole, fluconazole, itraconazole.
b. pyrimidine antimetabolites: flucytosine.
II. Systemic antifungal for mucocutaneous infections:
a. affect ergosterol (inhibit its synthesis): terbinafine.
b. inhibition of mitosis: griseofulvin.
II. Superficial:
affect ergosterol:
- pores formation: nystatin.
- inhibition of synthesis: miconazole, clotrimazole.
- others…
∙ Amphotericin B:
- Mechanism of action: alteration of cell membrane integrity leading to fungal cell death.
- Route of administration: IV infusion, intrathecal in meningitis,
can be used in eyes, joints, and in urinary bladder.
- Excretion: in bile.
- Activity: candida species, aspergillus, histoplasmosis.
- Side effects: anaphylaxis, hypokalemia, hypotension, anemia, fever, chills,
renal impairment, thrombophlebitis, convulsions.
Uses and side effects

Uses Side effects
Amphotericin B Systemic C.Albicans, C.Neoformens, Bake and Shake, superinfection,
I.V & I.T Aspergillus hypersensitivity, thrombophlebitis,
nephrotoxicity and anemia
Miconazole Candida, dermatophytes N&V, reversible liver dysfunction
Ketoconazole Candidia, dermatophytes, systemic N&V, hepatotoxic, rashes,
(Oral and IV) mycosis. The same as amphotericin gynecomastia, Cyt.P450 inhibitor
Fluconazole (Oral) Dermatopytes, candida, cryptococcus GI disturbances, rash, headache,
hepatotoxic, Inhibitor of Cyt.P450
Itraconazole Aspergillus, histoplasma GI disturbances, rash, headache
Flucytosine (oral) Candida and cryptococcus B.M depression
Griseofulvin Dermatophytes and tinea Hepatotoxic, causing porphyria

Antiviral Drugs
Classification
I. Drugs for herpes virus infection:
- Acyclovir, gancyclovir, vidarabine, uridine.
II. Drugs for hepatitis B and C viruses:
- Ribavirin, interferon.
III. Drugs for respiratory system:
- amantadine, rimantadine and also ribavirin.
∙ Acyclovir: 10 mg/kg/dose IV or oral every 8 hrs.

- Mechanism of action: inhibits viral DNA polymerase.
- Spectrum (activity): Herpes simplex, Varicella zoster.
The drug of choice in herpes simplex encephalitis.
- Route: oral, IV, topical.
- Side effects: renal dysfunction, GIT upsets, irritation action.
∙ Interferon:
Interferon
- Mechanism of action: interferes with cellular metabolic processes, such as RNA and
protein synthesis.
- Types:
Alpha: used in chronic HCV, HBV infection.
Beta: used in relapsing multiple sclerosis.
Gama: used in chronic granulomatous diseases.
- Side effects: influenza-like symptoms, anorexia, fatigue,
bone marrow depression,
confusion, seizures, alopecia.

Drug Dose Action Uses Side effects

I. Respiratory:
- Amantadine - 5-10 mg/kg/day,oral,twice -block viral membrane ptn - Influenza virus - Teratogenic
- Rimantadine - 5mg/kg/day, oral -" “ “ “ - “ “ -“ “ and GI upset
- Ribavirin -" “ & inhibits RNA - RSV, Hepatitis B,C -“ “ and anemia
synthesis
II. Anti-Herpes
- Acyclovir - 10 mg/kg/dose IV,PO-8 h
Inhibiton - HSV,VZV,EBV - nephrotoxic
- Gancyclovir - infants: 12 mg/kg/day IV-12 h of - CMV - neutropenia ,
- > 3y: 14-20 mg/kg/day IV-12 h Viral thrombocytopenia, retinal
DNA detachment
- Famcyclovir - 250 mg/kg/dose, oral - 8 h synthesis - HZV (acute) - nausea, vomiting
- Vidrabine - HZV (eye infection)
- Cidofavir - CMV retinitis
- penciclovir - HSV, HZV
III. Anti-HIV
- Zidovudine
- Didanosine
- Zolcitabine
- Chronic Hepatitis B&C, genital - fever, lethargy, BM
Interferon  wart, Kaposi sarcoma depression.
- relapsing multiple sclerosis

ß
 - chronic granulomatous tissues

Poisoning
➢ Management:
∙ Quick examination: A B C D E
∙ Resuscitation: A B C and other measures.
∙ History and examination
∙ Definitive care:
- Multisystemic support.
- measures against the poison: antidote, prevention of absorption, enhancement of
excretion.
N.B: Nine common agents that kill in low doses:

1) Ca channel blocker, (1-10 mg) nifedipine: hypotension and bradycardia.
2) Camphor, 15 ml (100 mg camphor): respiratory depression and seizures.
3) Clonidine, 0.1 mg: severe bradycardia.
4) Tricyclic antidepressants, 10-20 mg: CVS and CNS toxicity.
5) Opioids, 2.5 mg of hydrocarbone: respiratory depression.
6) LomotilTM (atropine and diphenoxylate, anticholinergic) ½ tablet: seizures and coma.
7) Salicylate, ½ teaspoon of wintergreen: cerebral edema.
8) Sulfunylureas, 1 tablet: severe hypoglycemia.
9) Toxic alcohols, 2.9 ml of 95 % ethyline glycol has been fatal.
Antidotes
Poison Antidote Dose
CO Oxygen 100 % or hyperbaric
Methemoglobinemia Methylene blue 1-2 mg/kg I.V over 10 min.
Organic phosphorus Atropine 0.1 mg/kg I.V every 30 min.
till papillary dilatation
Opiates, narcotics Naloxone 0.1 mg/kg I.V,
(morphine) may be repeated
Iron Deferoxamine 10-15 mg/kg/hr I.V infusion
Chlorpromazine Diphenhydramine 0.5-1 gm/kg I.V or I.M
I.N.H Pyridoxine 5 gm I.V
Lead EDTA or oral D- 250 mg/m2/dose
penecillamine I.M every 4 hrs
Cyanide Na nitrate, Na thiosulphate Depends on Hb level
Paracetamol N-aceylcystein
Salicylate Poisoning
- In a dose less than 150 mg/kg, no toxic reactions is expected.

- 150-300 mg/kg, mild to moderate.
- 300-500 mg/kg, severe.
- > 500 mg/kg, lethal.
∙ Phase I (12 hrs): stimulation of respiratory center  respiratory alkalosis with
compensatory alkaline urine (loss of bicarbonate, Na, K).
∙ Phase II:
II hypokalemia and aciduria.
∙ Phase III (6-24 hrs): dehydration, hypokalemia, progressive lactic acidosis.
- may progress to pulmonary edema, renal failure and coma.
Treatment:
1. Gastric lavage up to 4 hrs and activated charcoal.
2. Correction of dehydration and electrolytes disorders:
- sodium bicarb at 2 mEq/kg over 5 hrs.
- K administration even if serum K is normal.
3. Haemodialysis in case of:
- failure of urine alkalinization.
- patient with APOS.
- all patient with renal failure.
4. Management of pulmonary edema:
- head elevation.
- hypeventilation or ETI.
- mannitol 0.25 gm/kg/dose over an hour.

Varicella Zoster Infection

(Neonatal and Congenital)
I. Neonatal Chicken pox
- Delivery within 1 week before of after the onset of maternal varicella infection, frequently
results in a newborn developing varicella which may be severe.
- The initial infection is intrauterine, although the newborn develops clinical chicken pox
postpartum.
- If there is an interval > 1 week interval between maternal chicken pox and parturition, it
is likely that the newborn received sufficient transplacental antibodies to VZV to ameliorate
the neonatal infection.
- If the interval is < 1 week, it is unlikely to the newborn to have protective antibodies to
VZV and the neonatal chicken pox may be severe (hepatitis, encephalitis, pneumonia).
∙ Treatment:
- Acyclovir 10 mg/kg/dose every 8 hours I.V.
- VZIg: 1 vial I.M.
II. Congenital Varicella Syndrome
- The risk of transplacental infection is about 25% of fetuses, although not every infected
fetus is clinically affected.
- Up to 2% of fetuses whose mothers had varicella infection in the 1st 20 weeks of pregnancy
may demonstrate VZV fetopathy.
∙ Stigmata of Varicella-Zoster virus fetopathy:

1. Damage to sensory nerves:
- characteristic cicatricial skin lesions and hypopigmentation.
2. Damage to the optic stalk and lens vesicles:
- microphthalmia, chorioretinitis, cataract, optic atrophy.
3. Damage to cervical and lumbosacral cord:
- hypoplasia of an extremit, motor and sensory defects, absent deep tendon reflexes,
anisocoria, Horner's syndrome, anal/urinary sphincter dysfunction.
∙ Diagnosis of VZV congenital fetopathy:

- History of gestational chicken pox. - Clinical manifestations.
- Viral DNA. - VZV specific IgM antibodies.

Genetics
 Trisomy 21 (Down syndrome)
non-dysjunction (94 %)
∙ Typical Craniofacial appearance:
- round face and flat nasal bridge.
- upslanted palpebral fissure.
- epicanthic folds, flat occiput and 3rd font…
- brush-field spots in iris, low set ear.
- small mouth and protruding tongue.
∙ Other anomalies:
- single palmer crease, incurved little finger and wide gap between toes.
- short neck.
- hypotonia.
- congenital heart disease.
- duodenal atresia.
- congenital heart disease.
- Hiersh Sprung disease.
∙ Late Medical Manifestations:

- moderate to severe learning difficulties.
- delayed motor milestones.
- increased susceptibility to infections.
- short stature.
- visual impairment due to cataract and squint.
- increased risk of leukemia and solid tumors.
- epilepsy and Alzheimer.
 Trisomy 18 (Edward syndrome)

- low birth weight.
- prominent occiput.
- small mouth and chin.
- short stature.
- flexed overlapping fingers.
- Rocker button foot.
- cardiac and renal malformations
- low set ear.

Lymphoma, Leukemia, Tumor Markers
Pathology of Lymphoma
∙ Definition: it is a malignant proliferation of lymphoid precursor cells.

- It is the 3rd most common cancer in children, more common in males than in females.
∙ Types: Hodgkin's lymphoma
Non-Hodgkin's lymphoma (NHL)
Hodgkin's Lymphoma
- Age: 15-35 years. It is rare under 5 years.

- It has a slower growing rate than NHL.
- It is characterized by presence of neoplastic Reed-stenberg cells (RS cells) in reactive
lymph node infiltrate.
- Some cases shows evidence of previous EBV infection.
➢ Types of Hodgkin's lymphoma:

1. Lymphocytic predominant:
- All cells are mature lymphocytes or mixture of lymphocytes and benign histiocytes with
only occasional Reed-stenberg cells. (few RS cells)
- It affects 10-20 % of patients with the best prognosis.
2. Nodular sclerosing: the most common, affects 50-70 % of cases.
- Broad bands of collagen divides the involved L.N into nodular cellular areas.
- A specific cytologic features is clear spaces surrounding lacunar cells (shrunken
cytoplasm) which are variables of Reed-Stenberg cells.
3. Mixed cellularity: the second most common type, affects 40-50 % of cases.
- Cells are lymphocytes, plasma cells, esinophils, histiocytes, malignant reticular cells and
Reed-Stenberg cells.
- Foci of necrosis.
4. Lymphocytic depletion: is the least common, < 10 % of cases.
- Bizarre malignant reticular cells, Reed-Stenberg cells and few lymphocytes.
 Reed-Stenberg cells:
- contain 2 nuclei, each with a mirror image prominent nucleoli and nuclear membrane.
- cytoplasm is abundant.
 Hogkin disease arises in lymph nodes in almost all cases. Extranodal affection is <1%
occurring in spleen, liver, lungs and bone marrow.
 Spread is by direct anatomic extension to L.N through lymphatic vessels.

➢ Anatomic Staging “Ann Arbor staging”

Stage I: single site.
Stage II: more than one side of the disease, on one side of diaphragm.
Stage III: more than one side of the disease, on both sides of diaphragm.
Stage IV: Disseminated disease.
Non-Hodgkin's Lymphoma (NHL)
- It is divided according to histology, immunophenotype and cytogenetics into:
I. High grade lymphoma:

1. Lymphoblastic (30 %):
%) 90 % T cells and 10 % pre-B cells
- mostly presented with anterior mediastinal mass.
- In case if presence of > 25 % blast cells in BM, it is considered as ALL.
2. Mature B cells (Burkitt's or atypical lymphoma) (50 %):
- occurs in abdomen, head and neck, bone marrow and CNS.
- may grows very rapidly.
- endemic or early Africans, it is associated with EBV infection.
frequently affects jaw, which is a site rarely involved in sporadic disease.
3. Anaplastic large T cell lymphoma (<20 %):
- composed of large cells with very high mitotic activity.
II. Low grade lymphoma:

1. Diffuse small lymphocytic lymphoma.
2. Follicular small cell or mixed small and large cell lymphomas.
3. Other low grade lymphomas.

Pathology of Leukemia
- It is the most common malignancy of childhood.
- About 80 % of cases are acute lymphoblastic leukemia, 20 % acute myeloid leukemia,
others are rare.
- Chronic leukemia is uncommon in childhood.
➢ Types of Leukemia:
I. Acute leukemia:
1. Acute lymphoblastic (ALL):
- High risk ALL: T cell ALL & B cell ALL.
- Standard risk: Null cell.
FAB classification of acute lymphoblastic leukemia (ALL)

L1 L2 L3
Cell size small large heterogeneous large homogenous
Nuclear chromatin homogenous variable heterogeneous Finely stippled homogenous
Nuclear shape regular irregular Regular and round
Nucleoli absent one or more one or more
Cytoplasm scanty variable abundant
Basophilic cytoplasm slight variable Quite deep
Cytoplasmic vacuolation variable variable prominent
2. Acute non-lymphoblastic leukemia (ANLL):
FAB classification of acute myeloblastic leukemia (AML)

M1: myeloblatic, no maturation.
M2: myeloblastic, some maturation.
M3: hyperglanular promyelocytic.
M4: myelomonocytic.
M5: monocytic.
M6: erythroleukemia.
II. Chronic Myelocytic Leukemia:

- Adult form: chronic phase & blast crisis.
- Juvenile form: congenital leukemia.

Tumor Markers
(1) Carcinoembryonic antigen (CEA):
- used mainly for detecting recurrent or metastatic disease and for monitoring therapy in
carcinoma of pancreas, liver, colon, rectum, bronchi and breast.
(2) -fetoprotein (AFP):

- It is normally synthesized by the fetal liver.
- Present in plasma in:
1. Normal fetus.
2. Increased maternal AFP in cases of: fetal neural tube defect, twins, fetal distress.
3. Hepatic carcinoma, germ-cell tumors and testicular teratoma.
4. Viral hepatitis, cirrhosis or liver metastases.
- Raised amniotic fluid levels in:
1. Neural tube defect.
2. Congenital nephrotic syndrome.
3. Esophageal and duodenal atresia.
(3) Vanillyl mandelic acid (VMA):

- A high urinary levels is present in:
1. Tumors of sympathetic nervous system: pheochromocytoma, neuroblastoma.
2. Drugs: MAOI, phenothiazines, methyl-dopa, tetracycline.
3. Diet: bananas, vanilla, tea, ice cream and chocolate.
(4) Prostate specific antigen (PSA):

- It is raised in prostate cancer and in benign prostate hyperplasia.
(5) Human chorionic gonadotrophin (HCG):

- ß-HCG is raised in the first 2 days of pregnancy and peaks toward the end of 1st trimester.
- increased in: - Choriocarcinoma.
- Germ-cell tumors, teratoma and seminomas.
- 20% of breast cancers, especially with metastatic disease and occasionally
with pancreatic, ovarian and bladder cancers.
(6) CA 125:
- increased in: - ovarian, breast and liver cancers.
- pregnancy, cirrhosis and peritonitis.

(7) CA 153:
- increased in: breast cancer and benign breast diseases.
(8) CA 199:
- increased in: colorectal and pancreatic cancers and in cholestasis.
(9) 5-hydroxyindoleacetic acid (5-HIAA):

- increased urinary levels in: carcinoid syndrome.
- false positive in case of ingestion of foods high in serotonin e.g: bananas.
(10) Multiple endocrine neoplasia:

- MEN 1: parothyroid adenoma.
- MEN 2: A thyroid carcinoma.
B thyroid carcinoma & pheochromocytoma.
α-Fetoprotein
∙ Causes of increased α-fetoprotein level:

1. Twins.
2. Congenital nephrosis.
3. Incorrect gestational age.
4. Neural tube defects (anencephaly, spina bifida)
5. Hydrocphalus.
6. Hepatitis.
7. Intestinal atresia.
8. Threatened abortion.
9. Turner's syndrome.
10.Gastrochisis & omphalocele.
11. Patau's syndrome.
12. Posterior urethral valve.
13. Oligohydramnios.
∙ Causes of decreased α-fetoprotein level:

1. Trisomy. 2. Aneuploidy.
∙ Triple Blood Test:

α-fetoprotein, α-human chorionic gonadotrophin, unconjugated estriol.
- It is used for screening of Down syndrome and neural tube defects in
2nd trimester (16 weeks gestation).

The Egyptian Programmed Vaccination Schedule ‫يتاج تديث‬
Time Vaccine Route of administration

1st 3 months BCG 0.1 ml ID at the left arm
2nd month Sabine (polio) 2 drops on the tongue
3rdmonth DPT 0.5 ml deep I.M in the left thigh
6th month Hepatitis B 0.5 ml I.M in the right thigh laterally
H. influenza
9th month Sabine Booster dose
measles 0.5 ml S.C in the right arm
18th month Sabine Booster dose
DPT Booster dose
MMR 0.5 ml S.C
External program
3rd month: H.influenza vaccine 12th month: Pneumococcal vaccine.
3rd month: Typhoid. 4th month: Rota virus.
5th month: Chicken pox. 6th month: Hepatitis A.
 MCQs
1. In partial seizures, the drug of choice is… (carbamazipine)

2. In generalized seizures, the drug of choice is… (valproate)
3. In absence seizures, the drug of choice is… (..?)
4. In infantile spasm, the drug of choice is… (synacthen, ACTH)
5. The baby is born by flexors having the upper hand (flexed arms and feet).
And neutraliazation (flexors=extensors) occurs at.. (4th, 5th months).
6. Components of the motor neurons:
- motor cortex, basal ganglia, brain stem, cerebellum.
- spinal cord. - skeletal muscles. - receptors.
- CPK in skeletal muscles is … (ten times) than in cardiac muscles.
- Skeletal muscle is composed of.. (thousands) of muscle fibers.
- Skeletal muscle contain 1% glucogenesis.
- Range of insensible water loss per day.. (400…./../day)
- normal urine output/kg/hr is… 1.5 ml (2-4)
- Caloric requirements/kg/day is….. 120.
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Basics for Egyptian Fellowship of Pediatrics (step 1) CVS

Prepared by Dr. .. 1 Typed by M.A

Embryology & congenital anomalies

➢ Development of the ventricles:

➢ The truncus arteriosus:

Prepared by Dr. .. 4 Typed by M.A

Congenital Anomalies of the heart

Prepared by Dr. .. 6 Typed by M.A

∙ Factors modifying CO: HR & SV

∙ Preload: CVP = Lt ventricular end diastolic volume

Arterial Blood Pressure

➢ Regulation of the Arterial Blood Pressure:

➢ Classification (causes, types):

III. According to cardiac output:

IV. According to stage:

V. According to intravascular volume:

➢ How does shock cause death?

➢ Clinical Stages of Shock:

N.B: Causes of SHOCK:

Prepared by Dr. .. 13 Typed by M.A

Pathology of infective endocarditis

Acute Infective Endocarditis Subacute Infective Endocarditis

Pharmacology & Treatment

I. Digitalis Digoxin is the usually used.

II. α and β adrenergic agonists I.V only

IV. Afterload Reducing Agents (vasodilators) including ACE inhibitors.

VI. Chronic treatment with β adrenergic blocker

∙ Dosage: see above (p.5)

Management of digitalis toxicity:

Prepared by Dr. .. 24 Typed by M.A

II. Adrenergic Blockers

III. Renin-Angiotensin Inhibitors

IV. Calcium Channel Blockers

Prepared by Dr. .. 26 Typed by M.A

Prepared by Dr. .. 27 Typed by M.A

∙ Contraindications: severe sinus node, A.V block without pacemaker.

2. Verapamil: (Ca channel blocker)

3. Adenosine: (purinergic agonist)

Prepared by Dr. .. 30 Typed by M.A

Prepared by Dr. .. 31 Typed by M.A

III. Function of loop of Henle:

IV. Distal convoluted tubules:

Measurement of Renal Functions

• Syndrome of inappropriate ADH secretion (SIADH):

• Causes of ADH deficiency:

Prepared by Dr. .. 36 Typed by M.A

➢ Glomerular diseases pathogenesis:

➢ Classification of glomerular diseases:

∙ Types of nephritic syndrome:

Systemic lupus nephritis

- WHO classification is based on L/M, E/M, IF/M

Rapidly progressive (crescentic) GN

- Type I: anti-GBM (20%)

- It is similar to acute post-streptococcal GN, but fewer glomeruli are affected.

- By light microscopy: thickened basement membrane (tram-track appearance),

The Nephrotic Syndrome

Urinary Tract Obstruction

Tumors of the Kidney

Pediatric renal tumors represents approximately 7% of all childhood tumors.

Wilm's Tumor (Nephroblastoma)

Pharmacology & Treatment

I. Observation: - Temperature (infection) - Weight - Blood pressure.

II. Diet: - sodium restriction.

IV. Treatment of end stage renal failure: