CAUSES OF HYPERBILIRUBINAEMIA 11

UNCONJUGATED (Conjugated bilirubin <15% of total)

1- T Production: Hemolytic disease of the newborn(Rh & ABO incompatibility)

Membrane defect (spherocytosis andelliptocytosis)

Enzyme defect (G6PDI) Hemoglobinopathy ((x- thalssemia} Synthetic vii K administration Sepsis•Large cephalhematoma 2- Defective

transport: I Albumin (e.g. Nephrosis). Displacement of bilirubin from protein bindingsites (e.g. Ampicillin, Aspirin, Warfarin)

3- Defective uptake:

I Z,Y proteins "Gilbert disease" -4 AD, mild disease.4- Defective conjugation: Glucoronyl transferase enzyme:bsence (Criggler Najjar Type 1-4 AR).

Poor prognosiseficiency (Criggler Najjar type II-SAD).

Less severe than type I *Immaturity (Physiological jaundice). *Lack of stimulation (Cretinism)Inhibition (Breast milk jaundice) ~ Due to:

1- Pregnandiol & non-estrified fattyacids present in breast milk.

2- T enterohepatic circulation due topresence of 0 glucoronidase in breast

milk that deconjugate bilirubin. Bilirubin mayrise up to 10-30 mg/dl during the second weekof life and return to normal by 4-12 weeks with good general condition & weight gain.

CON.TIJGATFD (Conjugated bilirubin >15 % of total) 1-

Defective secretion of conjugatedbilirubin by hepatocytes:

Rotor and Dubin Jonson syndromes (AR) Neonatal hepatitis either sepsis,idiopathic or TORSCH

Metabolic as galactosemia, tyrosinaemiaor cx, antitrypsin deficiency

2- Defective excretion (Bile flow obstruction) Intrahepatic:

Congenital intrahepatic biliary atresia. Viral hepatitis

Extra hepatic: Congenital extrahepatic biliary atresia. Biliary tumours or stones. Inspissated bile syndrome: (prolongedunconjugated hyperbilirubinaemia leads to increase production of conjugated bilirubin bythe liver which accumulates in biliary canaliculiobstructing them---) changing the condition to conjugated hyper-bilirubinaemia).

N.B.The commonest causes of conjugated hyperbilirubinacmia are: 1- Idiopathic neonatal hepatitis. 2- Extra hepatic biliary atresia 3- a, antitrypsin deficiency

APPROACH TO DIAGNOSIS OF NEONATAL JAUNDICE

I- History: Maternal history:

Previous abortion or blood transfusion. Infection or drug intake during pregnancy.

Family history: Consanguinity Similar attacks

Perinatal history: Instrumental delivery --> cephalhematoma Prematurity Synthetic vit. K administration or drug intake.

Time of appearance of jaundice: Jaundice appear in the V day of life:

Hemolytic disease of the newborn (RH or ABO).

TORCH Jaundice appear in 2nd - 3rd day of life:

Physiological jaundice Criggler Najjar syndrome. TORCH

Jaundice appear in 4ch - 7 cn day of life: Delayed physiological jaundice Cephalhematoma. TORCH Neonatal sepsis. Hemolytic anaemias (G6PD 1, spherocytosis, ...............}

Jaundice appear after the first week of life: Breast milk jaundice. Congenital biliary atresia. Galactosemia. Neonatal hepatitis. Cretinism.

N.B. => (Cong.. biliary atresia, Neonatal

hepatitis and Galactosemia are usually associated with jaundice which persist beyond neonatal period).

II- examination: To D.D. conjugated from unconjugated:

Colour of sclera => Lemon yellow ---> unconjugated.

=> Olive green ---) conjugated. Urine and stool => Normal urine ± dark stool --> unconjugated.

=:> Dark urine and clay stool -4 conjugated.

To detect the level,: If jaundice reaches to certain body sites: Face ---> 5 mg/dl • Chest 10 mg/dl • Thigh 15mg/dl • Sole 20 mg/dl

* To detect the cause: Seram Biiirubin

Uacoai. HvpcrbilirabinaemiaAb % and TReticulocytic count.

Present (hemolytic) Absent (non hemolytic) Blood grouping. • 'I'4 & TSUfor baby & mother. • Sepsis screen

Coomb's test.Investigations forspherocytosis and G6PD.

Sepsis screen

Coal. Hvperbilrubinaemia Liver function tests. Liver scan (HIDA scan). Liver biopsy.

Metabolic screene.g. galactosaernia

•TORSCH screen* Sepsis screen.

I PHYSIOLOGICAL .:4UNDICE I Aetiology: 1- Immaturity of Glucuronyl transferase enzyme. 2- Short life span of neonatal RBC's.3- Low Y & Z protein levels in liver cells during the first week of life.4- .G breast milk leads to I calories & dehydration -4 T entE:rvhepatic circulation-5- Other factors: polycythemia, cephalhetnatorna, bruises.

Incidence: The commonest cause of neonatal jaundice occurs in40% of full term & 60% of pretean.

Characters: Unconjugated hyperbilirttbinaemia. Mild to moderate rise of serum bilirubin. Usually start in the 2°`t or 3rdday of life. Usually disappear within 1-2 weeks. No associated problems, loo risk of kernicterus.

DM.: Physiological jaundice must be differentiated from other causes of jaundice.

Physiological Pathological Jaundice+~ t 2ndar 3`d day (4-7 •Anytime (even V * Duration

• About one week infull term

• May be longer

* Rate of < Stngfdi per day. • > Smg/dl per day* Peak < 12 mg/dl (15 in • May be higher.* Type Unconjugated Unconjugated or

conjugated

~ 1 1 1: Physiological jaundice usually resolves

spontaneously, in exaggerated cases phototherapy may be needed.

N.B.1- Exaggerated physiological jaundice:

M Serum bilirubin > 15 mg/dl.• Risk factors: Male sex, breast

milk feeders and polycythemia. 2- Prolonged physiological jaundice:

11 Physiological jaundice persists more than 2weeks. Risk factors: Cretinism, pyloric stenosis and constipation

(T enterohepatic circulation). 3- Physiological jaundice ofprematures:

11 More common. Late onset (± 4`h day). Higher level (± 14 mg/dl) Prolonged duration (± 2 weeks).

TREATMENT OF NEONATAL JAUNDICEI- Indirect (unconjugated)

hyperbilirubinemia1- PHOTOTHERAPY:

Idea: Exposure of neonate with unconjugated hyperbitirubinemia to blue or

white light with wave length (420-470 nm)will convert unconj. bilirubin

to non toxic photoisomers which are excreted inurine and bile.

Indications: 1- Rise of bilirubin to high levels (but belowthe critical levels when kernicterus may occur).

2- During waiting for exchange transfusion.

3- Prophylactic in: • Very low birth weight. Severely bruised neonates. Immediately after birth if Rh incompatibility is suspected.

Contraindications: Direct hyperbilirubinemia -~ Bronzed baby syndrome.

Procedure: The baby should be completely exposed covering only eyes and genitalia.

Exposure should be continuous with short intervals for feeding (Excess fluid is necessary to prevent dehydration).

Change the position of the baby every now and then.

Recording of temp. is important every 6 hours.

Discharge from phototherapy when bilirubin level is low enough that no risk ofkernicterus will be present:

13 ± 0.7 mg/dl in full term.10 ± 1.2 mg/dl in preterm.

Side effects: I- Hyperthermia . 4- Dehydration2- Skin rash 5- Damage to eye or genitalia3- Hypocalcaemia in prematures. 6- Diarrhea (due toT bile salts in stool).

2- EXCHANGE TRANSFUSION: Idea:

Removal of excess unconjugated bilirubin. In cases of Rh_ incompatibility it corrects anaemia and the circulation.

Indications:

1- In hemolytic disease of the newborn:Cord bilirubin > 5 mg/dl.Cord hemoglobin < 10 gm/dI.Rapid rise of serum bilirubin(> i mg/dl/hour or > 5 mg/dl/day).

Bilirubin level exceeding:- I O mg/dl at first day. - I S mgldl at second day.

History of kernicterus in a sibling.2- In any cause:

Serum bilirubin exceeding critical values (20-25 mg/dl).

Early signs of kernicterus_ Procedure:

Blood used is 0 -ve compatible with both maternal and neonatal blood.

Amount needed is double the blood volume of the neonate (2 x 85 ml/kg).

Small amount of blood (10-20 ml) is removed and replaced by equal amount ofthe new blood every few minutes_

Side effects: 1- Hazards of umbilical catheterizatione.g. embolism, thrombosis, sepsis & portal hypertension. 2- Hazards of blood transfusion. 3- Heart failure (TT load on the heart). 4- Hypocalcaenua, hypoglycaemia, hyperkalaemia.

3- OTHER LINES OF TIT: Phenobarbitone:

Induce glucuronyl transferase enzyme esp. in Criggler Najjar syndrome type II_

Treatment of the cause: TIT of sepsisAvoid drugs which displace bilirubin from plasma protein binding sites..

TFT of hypothyroidism.•In breast milk jaundice: Stop breast feeding

for 24-48 hours only (jaundicewill disappear and not recur).

II- Direct (conjugated) hyperbilirubinaemia 1- TIT OF THE CAUSE: * Sepsis, Galactosaemia, . .

* Surgery for biliary atresia (Kasai operation). 2- NON SPECIFIC'I"I"I': * Corticosteroids

Phenobarbitone. Doubtful results

Choleretics (e.g. cholestyramine)

j. Other indications for exchange transfusion: - NEC- Neonatal sepsis. - Polycythaemia.- Anaemic heart failure.

ADefiru'on:Yellowish discoloration of brain cellsespecially basal gangli::to deposition of unconjugated bilirubin. It is better namedbilirubin encephalopathy (as kernicterus is apathological term).

~It Aetiology:1- Level of serum bilirubin exceeding critical values (10 in 1'` day, 15 in 2"d day

then 20 mg/dl for hemolytic and 25 mgldI for non hemolytic). Howeverkernicterus may occur at lower levels than usual if certain factors are present: Factors TT permeability of BBB:

Sepsis • Prematurity

Hypoxia • Acidosis. Factors displace bilirubin from albumin:•Drugs (Ampicillin, sulpha, warfarin) • Hypoalbuminaemia

2- Duration of exposure to the high biliivbin level: The longer the duration the more riskof kernicterus.

*CM: Acute bilirubin encephalopathy: Can be divided into three phases:1- Hypotonia, lethargy, poor suckling and high pitched cry (resembling sepsis or ICH)2- Hypertonia, rigidity, opisthotonus, fever, convulsions and bulged fontanelles. Many infants die in this phase, all infants whosurvive develop chronic bilirubin encephalopathy.

3- 1 lypotonia replaces hypertonia after aboutone week.

Lucid interval: Usually asymptomatic phase may last weeks tomonths in survivors from previous stage.

Chronic bilirubin encephalopathy: The full - blown picture of kernicterus (permanent).

M.R., C.P., dental dysplasia, deafness, choreoathetosis, squint (either all or some of them).

A n'Ianagement:1- Prophvlaxis:

Prophylaxis is the main ttt for kernicterusit can be achieved TTT of unconjugated hyperbilirubinaemia bythe appropriate method (phototherapy, exchange, ).

•Prevention of other risk factors:e.g. sepsis, acidosis, hypoxia, ............ 2- TTT:

No ttt for kernicterus, only rehabilitation: TTT of convulsions, chorea, rigidity.•Management of MR according to degree

(mild/moderate/severe/profound) Q. How to predict kernicterus?

1- MRI brain.2- Brain stem auditory evoked response.

I KERNICTERLS

V- BLOOD DISEASES OF THE NEWBORNNEONATAL ANAEMIA

1- Blood loss ~ Aetiology* Prenatal causes:- Feto-Fetal transfusion- Feto-maternal transfusion - Placenta previa.* Postnatal causes:- Causes of neonatal bleeding esp. hemorrhagicdisease of the newborn (see page 134)- Frequent sampling.- Cephalhematoma, subgalial hematoma and other injuries.~ Investigations:1.1, RBC's and HbN. or TT reticylocytes.Normal bilirubin.For the cause.

2- Hemolvsis

•Immune hemolysis:Rh, ABO or minor groups incompatibility"Hemolytic disease of the newborn"

•Non-immune hemolysis: - Heridetary as G6PD1, athalassaemia or congenitalspherocytosis.- Acquired as DIC, sepsis orvitamin E deficiency.

11 RBC's and Hb. TT reticulocytes. TT bilirubin.For the cause.

3- 1 RBC's production RBC's and Hb. reticulocytes. Normal bilirubin. For the cause.. C/P: 1- Of anaemia (pallor, irritability, ....)2- Of the cause.

Treatment: 1- Treatment of the cause.2- Blood transfusion (20 ml/kg) or packed RBC's transfusion (10 mUkg) in severe anaemia or blood loss.

3- Recombinant human erythropiotein in anaemia associated with prematurity. N.B.. b

4) Normal Hb at birth is 17-20 gm/dl.After birth 02 saturation in blood TT soinhibition of erythropoiesis occur tillHb falls to low levels (10-11 gm/dl) at

Congenital infectionsCongenital leukemiaCongenital pure red cellanaemia (Diamond

which erythropoiesis is restimulated.These low levels occur about 6-12 weeksafter delivery and called physiologicalanaemia of infancy.

C) Hemolytic disease of the newborn "Erythroblastosis foetalis"

Hemolysis of neonatal RBC's due to transplacental passage of maternalantibodies active against fetal RBC's.

It includes Rh, ABO & minor group isoimmunization.

X tso-tmnnut~n

~~ Pathogeoc~js:1- 85% of the population are Rh +ve (DD or Dd)

i.e. having D antigen in their RBC's. The remaining 15% are Rh -ve (dd).

2- Escape of small amount of Rh +vc foetal blood(inherited from Rh +ve father) to thecirculation of Rh -ve mot!" may occurduring pregnancy, abortion or at delivery -4sensitization of the Rh -ve mother --->formation of maternal anti-Rhantibodies (usually of IgG type which cross theplacenta) -3~ Destruction of foetal RBC's_

3- The first baby usually escape hemolysis as sensitization usually occur near time of delivery (late time to transmit antibodies to the baby), but the l ~ baby may be affected if the mother isalready sensitized (e.g. previous abortion of Rh +ve foetus or previous transfusion of Rh +ve blood).

4- Not every Rh incompatibility leads to hemolysis as:

Some Rh +ve fathers are heterozygous (Dd) so they may have Rh -veoffsprings.

Not all deliveries are associated with fete-maternal transfusion.

The ability of Rh -ve mothers to form anti -Rh antibodies are variable.

Associated ABO incompatibility may protect against F -_ncompacibility asentrance of foetal blood grr -D A or B will be rapidly destructed in bloodgroup 0 mother before s' mutation of anti-Rh formation.

Clinical picture: According to severity, different presentations may occurI- Hydrousfoetalis (the most severe form) -4 In utero:

Generalized oedema. Severe anaemia (pallor} and anaemic heart failure.

Hepatosplenomeealy Most cases die in utero or shortly after birth.

2- Icterus p,>"avis neonatorum (less severe) ---) At birth.:

Severe anaemia (gradually increase). Hepatosplenomegaly. Marked unconjugated hyperbilirubinemia (gradually TT) If nc . reatedurgently --4 kernicterus_

untreated cases usually die in the neonatal period.

3- Acmdv~tic anaemia (mild form) -+ Early neonatal:

Mild anaemia

± splenomegaly Mild unconjugated h rbilirubinemia. The best progiostic type.

~D.D:1- Other causes of neonatal anaemia. 2- Other causes of neonatal jaundice-

3- Other causes of hydrops foetalis (Generalized subcutaneous oedema, pleuraleffusion and ascitis) as -~ • Severe hemolyticdiseases.

Severe liver diseases. Congenital infection. Congenital nephrosis. Chromosomal anomalies;.

~ Manag - men of Rh-incom i ati v il' I- During pregnancy:

1- Screening of all pregnant females for Rh group=:!> If Rh +ve -> nothing.=> If Rh -ve check father's Rh group (If -ve nothing)

2- If the mother is Rh -ve and the father is Rh +ve: U Maternal history

1First pregnancy with no previous abortion orblood transfusion.No interference except giving the mother anti-Dinjection. (after 28 w. gestation and within 72hrs after delivery)

Subsequent pregnancies orprevious abortion or previous blood transfusion.

uDetermine IgG titre of antiRh in maternal blood by

indirect coomb's test at 12-16w. gestation.

Low titre not rising High titre or rising at serial measures titre at serial measures(20, 28, 32, 36 w.) (20, 28, 32, 36 w.) 1

Perform amniocentesis to checkbilirubin level in amniotic fluid.

fI- After delivery: Investigations: The same investigation for indirect (unconjugated) hyperbilirubinemia =:> see before.

Treatment: The same lines for indirect (unconjugated) hyperbilirubinemia (exchange, phototherapy, ....) ~ see before.

HBO rso-bmucnizntion Pathogenesis: 1- If the mother is group (0) her blood willnaturally contain anti-A and anti-B antibodies which can destruct foetal RBC's if the baby is blood group A or B.

2- Anti-A and Anti-B are of IgM type which can not cross the placenta, however in 10-15% of cases these antibodies are of IgG type which can cross the placenta-4 foetal RBC's hemolysis.

3- As the AB antibodies are naturally present(in contrast to anti-Rh), so the first babymay be affected.

Clinical picture: • Mild neonatal anaemia and jaundice -4 good prognosis.

Investigations: • As investigations of Rh-incompatibility after delivery.

Treatment: •Phototherapy • Exchange is rarely needed.

I NEONATAL BLEEDING i

I~ Bleeding in healthy baby* Bleeding in sick baby

1- Hemorrhagic disease of newborn. 2- Swallowedmaternal blood.3- Inherited coagulation defects:e.g. hemophilia A, B or C and Von Willebrand disease.

4- Inherited thrombocvtopenia: e.g. TAR syndrome (thromb(yytopenia absent radius)

5- Immune thrombocytopenia:Due to transplacental passage of maternalantibodies against foetal platelets e.g.maternal SLE.

1- Consumption coagulopathy (DIC). 2- Necrotizingenterocolitis (NEC) 3- Surgical emergencies:e.g. volvolus, intussusception.

4- Stress gastric ulceration. 5- Severe

liver diseases.

Hemorrhagie disease of the newborn• Definition: Self limited hemorrhagic

disorder in early neonatal period due to deficiency of vitamin K dependant clotting factors (II, VII,IX, X).

Incidence: * About 1:3000 live births. Preterm more affected > full term.• Breast feeding more affected > artificial feeding (Breast milk is deficient in vit. K)

Pathogenesis: Transplacental vit. K is usually depleted by the 2"d day of life while endogenoussynthesis of vit. K is delayed to the 5"' day due to absence of intestinal bacteriaflora which synthesize vit. K in the neonate +immaturity of neonatal liver.So, hemorrhage usually occurs from 2"d - 5`hday.

Other causes of vit. K deficiency e.g. prolonged antibiotic therapy ormalabsorption may lead to late onset hemorrhagic disease.

Clinical picture: Bleeding from different sites (GIT, umbilicalstump, urinary or rarely intracranial bleeding).

Resultant anaemia (pallor, irritability, )

Investigations: Normal bleeding time and platelet count. Prolonged clotting time, P.T. and P.T.T. Deficiency of vit. K dependant factors (II, VII, IX, X).

D. D.: Other causes of neonatal bleeding (see before) esp. swallowed maternal bloodwhich can be diagnosed by Apt test (foetal blood contains HbF which resistdenaturation by Alkali opposite to maternal blood which is easily denaturated byAlkali)

Prophylaxis: Administration of natural vitamin K 1 mg IM to all neonates at birth.

TT 1- Vit. KI (natural) 1-5 mg LV daily ± plasma transfusion. 2- Blood transfusion in severe bleeding to correct anaemia.

171- GUT PROBLEMS OF THE NEWBORN l

7~ Vomiting in doing well baby: Swallowed amniotic fluid. Swallowed maternal blood. Feeding disorders e.g.over feeding, aerophagia

Cow's milk proteinallergy.

Gastro-esophageal reflux. Congenital pyloric stenosis.

I NEONATAL VOMITINGI NEONATAL DIARRHEA

1- Non-infective diarrhea: Dietetic causes: overfeeding, concentrated formulae or under feeding "starvation diarrhea"

Cow's milk protein allerav. Lactose intolerance. Iatrogenic diarrhea: laxatives given to the baby or the mother (secreted in breast milk).

2- Infective diarrhea: (Uncommon)* Bacterial ~ Viral

Definition:

Syndrome of acute intestinal necrosis of unknown cause usually affects sick prematureswith high mortality rate.Risk factors: 1- Prematuriy --> the most important factor for NEC. 2- Perinatal asphyxia.3- Polycythaemia.4- PDA.5- Cocaine addicting mothers. 6- Cyanotic heart diseases.7- Congenital GIT anomalies.8- Catheterization ofthe umbilicus. 9-

Non breast Milk feeding.10- Hypertonic Milk formuolae.

* Vomiting in sick baby: Surgical problems Congenital intestinal obstruction e.g. esophageal atresia, meconium ileus,...

Acquired intestinal obstruction e.g. NEC and intussusception.

Medical problems ~ Infection e.g. septicaemia, pneumonia, ~ Increase intra cranial tension e.g. meningitis, ICH,

~ Inborn errors of metabolism e.g. Galactosaemia.

Pathogenesis:1- Ischaemia and mucosal damage esp. In terminal ileum and proximal colon.2- Aggressive, rapid enteral feeding will devitalize the already weak intestinal wall --> sloughing and injury of the intestinal wall.

3- Superadded infection esp. with gas forming organisms ~ Gas formation within the bowel wall-~ extensive bowel necrosis and septicaemia -> perforation ± peritonitis. Other organisms may contribute to NEC e.g. staph, strept, corona virus & rota virus.

A Clinical picture:I- Speticaemic manifestations:

1- Poor feeding and hypothermia. 2- Lethargy and depressed reflexes. 3-

Hypotension and shock. 4- Attacks of apnea and acidosis.

II- Abdominal manifestations:1- Bilous vomiting and brown gastric aspirate.2- Abdominal distention and abdominal wall tenderness. 3- Ileus "absent intestinal sounds". 4- Bloody stool eitheroccult or obvious blood.

Investigations: 1- X-ray abdomen:

Pneumatosis-intestinalis --4 Gas in the intestinal wall.

Gas in the portal vein.• Pneumo-peritoneum (gas under

diaphragm) ~ If perforation occurs. 2- Sonar abdomen:

Portal venous gas.3- Laboratory findings:

The usual triad is: thrombocytopenia, hyponatraemia and metabolic acidosis.

Stool examination for occult blood.~~ D.D.:

Other causes of neonatal vomiting. Other causes of neonatal bleeding.

Prevention: 1- Prevention of risk factorss e.g. ttt of sepsis, prevention of prematurit}'. 2-Cortecosteroids if administrated prenatalor early postnatal. 3- Breast feeding my reduce the incidence of NEC !.

Treatment: 1- Stoppage of enteral feeding: With

nasogastric suction. Give IV fluids or TPN. 2- Antibiotics (Ampicillin/GaramycinlMetronidazol) 3- Supportive therapy:

Resp. ---~ 02, mechanical ventilation if needed.

CVS -4 Blood transfusion + removal of umbilical catheter.

Metabolic -~ • Correction of acidosis (Na HC03)

•Correction of hyponatraemia.4- Surgical ttt: • If perforation occurs.

(NEONATAL CONVULSIONS Definition:

Uncontrolled neural discharge leads to abnormal conversion of the potential energy of the neurons into kinetic energy.

Aetiology: I- CNS causes:

Hypoxic-ischaemic encephalopathy (HIE) -~ the most common cause.

Bilirubin encephalopathy (Kernicterus). CNS infections (meningitis, encephalitis,....)

CNS anomalies (cerebral dysgenesis). Intracranial hge (ICH).• Neurocutaneous syndromes

(Neurofibromatosis, Tuberous-Sclerosis, ........). 2- Metabolic causes:

Hypoglycaemia (< 40 mg/dl) -4 causes P. 153 Hypocaycaemia (< 7mg/dl) -* causes P. 153 Hypomagnaesemia (< 1.2 meq/L) Hyponatraemia (< 130 meq/L) or hypernatraemia (> 150 meq/L)

Pyridoxine (B6) deficiency. Amino acidopathies (phenyl ketonuria, urea cycle defect, maple syrup urine disease, )

3- Drub related causes: Drug withdrawal e.g. maternal narcotics or heroin addiction

• Drug causing convulsions e.glarge dose theophylline. 4- Other causes:

Familial (AD benign condition). Idiopathic.

Manifestations:1- Onset of convulsions:

151 day of life: e.g. HIE, Drug withdrawal and metabolic.

15` week of life: e.g. ICH and metabolic. After the 15` week: e.g. meningitis.

2- Types of convulsions: Subtle convulsions: (50%) -4 alone or associated with other types.Repetitive:- oral movements (suckling, chewing, ...)

- eye movements (blinking, nystagmus, ...)- limb movements (pedaling, ....)

or - apnea (associated with T HR in contrast to apnea due to respiratory

cause which is associated with ~ HR).

Tonic convulsions: Rigid posturing of the body (focal or generalized).

Clonic convulsion: Rapid alternating contraction and relaxation of muscles(focal or generalized)

Myoclonic convulsions: Sudden synchronous shock like movements of UL or LL.

Combined (more than one type): e.g. Tonic-clonic convulsions.

~ Approach to diagnosis:~- History: 1- Onset, frequency and duration of convulsions.2- Perinatal history: Asphyxia, birth trauma, cyanosis, drugs, .......................3- Family history: Amino acidopathies, previous Rh isoimmunization, familial or Neurocutaneous syndromes.

~- Examination:1- Physical exam: e.g. trauma, signs of infection, kernicterus, congenital head anomalies.

2- Neurological exam: e.g. signs of T ICT, meningeal irritation, type of convulsions.

~- Investigations:1- Investigations for metabolic causes:

Serum Ca, Mg, Na, glucose, Tests for aminoacidopathies.

2- Investigations for CNS causes: CSF for infection & bleeding. X-ray & CT skull (trauma, T ICT, hge).

~ - D.D.:Neonatal convulsions must not be mistakenwith Jitterness which is tremor likemovement of a limb which can be stopped byholding that limb "opposite toconvulsions". Jitterness is associated withhypoglycemia, hypocalcemia and may occur innormal neonates.

~ Treatment:

A- Treatment of the attack:1- 02 therapy, IV fluids & suction of secretions.2- Anticonvulsant drugs: Phenobarbiton 10-20mg/Kg. IV (loading)_

Improved No-improvementPhenobarbiton (maintenance) Phenytoin (loading)

3-5 mg/Kg/day. 10-15 mg` /Kg.IVImprovement No improvement

Phenytoin (maintenance) Diazepam 0.3 mg/kg IV3-5 mg/Kg/day. J. No

+ Diazepam continuous infusion

B- After controlling the attack:1- Treatment of the cause e.g. Ca, glucose, antibiotics, ..........................2- Trial of 50 mg pyridoxine IV is advisable in resistant cases.3- if no response after treatment of the cause or the cause is not found continue on

anti-convulsant drugs till complete physical,

neurological and EEG examination.

VIII- RESPIRATORY PROBLEMS OF THE NEWBORNNEONATAL CYANOSIS

Definition: Bluish discolouration of skin and mucus membranes due to presence of morethan 5 g/dl reduced Hb in blood.

It may be peripheral (not affect the tongue) or central (affect the tongue)

Causes: 1- Cardiac: Congenital cyanotic heart diseases ~ SevereH.F.

2- Respiratory: Causes of severe respiratory distress (see later).

3- CNS: Causes of central respiratory depression (see later).

4- Metabolic: Methemoglobinaemia

• D.D, of the cause of cyanosis:Breathing pattern

1- Hypoventilation 2- Normal

3- Resp. distress

l Hyperoxia test(response to 100% 02 for 10 min.)

Improvement lCNS Methemoglobinem

iaChestIConfirmed

bypresence ofconvulsions

Confirmed bymethemoglobin levelin blood.

Confirmedbypresence of

air entry and by X-ray chest

CVSl Confirmed by

presence of murmers and by ECHO.

I NEONATAL APNEA..~ Definition: Cessation of respiration:

kr For any period if associated with cyanosis and bradycardia.

Or * More than 15 seconds with or without cyanosis and bradycardia. Causes: 1- Apnea of prematuritv:

Attacks of Apnea in prematures (< 34 week gestation) occurs mainly between the 2"d andthe 5`h days of life.

Mechanism:• Central causes (40%): Respiratory center immaturity. 4 Obstructive causes (10%): Passive neck flexion. Mixed causes (50%): Due to both central and obstructive causes.

2- Pathological apnea: (A lot of causes):As respiratory & CNS causes of cyanosis.

) nvestigations: For the cause (Discuss).~~ Treatment: 1- Treatment of the cause:2- Treatment of the attack:

i- Start with ~ 4 Avoid neck flexion or extension and oral feeding.

Tactile stimulation.ii- If no response -~ ~ 02 therapy. -,~-

Suction of secretion. ~ Umbu-bag ventilation Drugs: (Aminophylline, Caffeine citrate).

iii- If no response ~~ Mechanical ventilation.I NEONATAL RESPIRATORY DEPRESSION Manifestations:

Slow irrigular respiration ± cyanosis. Apneic episodes. Disturbed consciousness ± coma. (It is also called RD due to CNS failure)

Causes: CNS anomalies. CNS narcosis (Maternal narcotic drugs or anaesthesia shortly before delivery).

CNS damage (1CH, HIE, Kernicterus, Trauma_..).

(NEONATAL RESPIRATORY DISTRESS* Grades of RD: -->

Grade (I) : Tachypnea + working alae nasiGrade (II) : Intercostal & subcostal retraction. Grade (III) : Grunting. Grade (IV) :Cyanosis.

Causes of RD:i- Pulmonary causes:

Hyaline membrane disease (infant respiratory distress syndrome).

Transient Tachypnea of the Newborn (TTN). Aspiration syndromes (Meconium aspiration, Milk aspiration, .......................).

Air leak syndromes (pneumothorax, pneumomediastinum, ...)

Pneumonia (congenital or acquired). Congenital lobar emphysema * Pleural effusion.

Pulmonary hypoplasia * Pulmonary hge.

Lung cysts ~ Lung collapse.ii- Extrapulmonary causes:

Upper airway obstruction ---.) (Bilateral choanal atresia, macroglossia, ..............)

CVS ---) H.F. (due to severe VSD, PDA, ...) Hematological --~ Anaemia or polycythaemia. Metabolic -4 Hypoglycaemia, hypothermia or acidosis. GIT -4 diaphragmatic hernia, GERD and tracheo-esophageal fistula.

respiratory Distress S rome"Hyaline membrane disease"

Definition: A syndrome of respiratory distressoccurs in the newborn due to surfactant deficiency. RDS is the commonest cause of neonatal death.

Aetiology: # Conditions associated with I synthesis of surfactant:

1- Prematurity: The smaller the gestational age the higher the incidence of RDS

(60% of prematures < 28 weeks gestation develop RDS).

2- Infant of diabetic mother: Cortisone is very essential for lung maturity.

Very low cortisone level is present in infant of diabetic mother (try tohyperinsulinism)

3- Cesarian section and precipitate labour: As stress of delivery is essential for surfactant production and enhancement of lungmaturation. 4- Other risk factors: Perinatalasphyxia / 2"d twin / male sex / antipartum

hge.

Patho-physiology 1- Normally: Surfactant is produced bypneumocytes type II after the 20 weeks ofgestation, its main action is to decrease thesurface tension within the alveoli to preventtheir collapse during expiration.

2- In RDS: A- .L surfactant ->T alveolar surface tension ---> collapse.B- Collapse (atelectasis) ->I Pa02, T PaC02 & IpH ---> vasoconstriction of

pulmonary blood vessels --> Alveolar hypoperfusion -->I metabolism ofpneumocytes type II ~.~ surfactant -~ vicious circle.

~~ Pathology: Macroscopic: The lung is purple in colour, liverlike consistency & sinks in water.

• Microscopic: Extensive atelectasis with oesinophilic membrane lining! alveoli (Hyaline membrane).

C/P: Suns of RD (Tachypnea, grunting, ....) develop within 12 hours after birth and progressively I I to reach peak in the 3rd dayof life.

`~= On auscultation -4 May be normal, however severe cases show diminished air entry ± bilateral fine basal crepitations.

Courses • In mild cases gradual improvement occurs from the 3rd day.

In severe cases death or

complications may occur.~~ Complications:

Shock • PDA • Pneumothorax • ICH • Chronic lung disease.

Investigations: Prenatal diagnosis Lecithin/sphingamyelin ratio in amniotic fluid--> • If > 2 -j No Risk of RDS.

If 1-2 -~ Risk of RD

If< 1--4T Risk of RDS.

Saturated phosphatidyl choline in amniotic fluids If > 500 µg /d1= immature lung.

Post natal diagnosis: 4 Chest X-ray: • Early: diffuse reticulo-nodular infiltrate "Ground

glass appearance" + air bronchogram.

Late: white lungs "opacification ofboth lungs"

ABG's: • Early:. Pa0 2. Late: .l- Pa02 + TPaC02 + IpH.

Shake test: • 0.5 ml gastric wash + 0.5 ml alcohol and shake well.

Risk of RDS is inversely proportionate to amount of bubbles.

D.D.: Causes of neonatal RD Management of RDS: i- Prevention of RDS:1- Avoid risk factors: •Avoid unnecessary C.S. • Control of

maternal DM. 2- Maternal eIucocortecoidtherapy:

Action -4 Glucocortecoids TT surfactant

production and accelerate lung maturity. Indications ~ * High risk mothers (< 34 w.gestation)

* .l, lecithin/sphingomyelin ratio in amniotic fluid.

Contraindications ---> Chorioamnionitis and maternal DM.

Dose ---~ Betamethazone 8 mg/8hrs for 24-48 hours before delivery.

ii- Treatment of RDS:1- Incubator care: Every neonate with respiratory distress should be admitted to NICtI ~\,ith frequent monitoring of vital signs, 02 saturation, ABG's, ................

2- Supportive measures: Respiratory support by 02 therapy --> If persistent low 02 saturation or cyanosis give continuous positive airway pressure (CPAP) --> If no improvement -4 Mechanicalventilation.

Feeding support -> begin with IV fluids -->if oral feeding can't be toleratedwithin 4-5 days total parenteral nutrition is advised.

Correction of hypotcnsion or anaemia -> whole blood transfusion 10 ml/kg.

Correction of metabolic acidosis by NaHC03 1-2 ml/kg IV.

3- Specific treatment: Antibiotics: should be given as it is difficult to differentiate RDS from congenital pneumonia.

Surfactant ttt: - Either preventive in VLBW after birth or as a therapy for

RDS as early as possible.- Types of surfactant are human,bovine or synthetic (exocerf). -Dose 5 ml/kg repeated after 12 hrsthrough endotracheal tube. -Complicated by pulmonary hge.

Prognosis: Poor prognosis with lower gestational age (death rate about 50%in neonates < 1.5 kg weight).

Transient 7aehypnea 4f 9he Newborn Transient respiratory distress occurs mainly infull term neonates.

Mechanism -4 Delayed resorption of foetal lung fluids by pulmonary lymphatic

system which occur mainly after cesarean section. C/P -~ • Mild RD occurs within few hours after birth (no grunting or cyanosis)

Usually improves spontaneously within 2-3 days.

X-ray chest ~ • Prominent vascular markings. Fluid in lung fissures.

TTT (Supportive) -~ • 02 (low concentration) ± IV fluids till improvement

MeconiumAspiration Severe respiratory distress occurs mainly in post mature or full term neonates exposed to severe asphyxia.

Mechanism -~ 1- Intrauterine asphyxia -4 relaxation of anal sphincter ~

meconium stained amniotic fluid.2- At birth -~ meconium aspirationto lungs ~

Areas of complete bronchiolar obstruction (collapse).

Areas of incomplete bronchiolar

obstruction (emphysema).3- try infection of the lungs + chemical irritation

C/P -~ • Severe RD with grunting and cyanosis. Meconium staining of nails, umbilicus, limbs, ....

X-ray chest ---) • Hyperinflated lungs ± pneumothorax.

TTT ---> • Supportive care, IV fluids, 02 & ventilation.

Death rate > 30%.

q IN-ABNORMAL GESTATIONAL AGE AND BIRTH WEIGHTI

1- Premature (Preterm): Infant born before 37 w. gestation regardlessto his weight.

2- Full term: Infant born between 37-42 w. gestation regardless to his weight.

3- Post mature (post term): Infant born after 42 w. gestation regardless to his weight.

4- Small for date (small for gestational age): Infant with birth weight < 10`h percentile of expected from his gestational age.

5- Appropriate for date:Infant with birth weight between 10`h and 90`h percentile of expected from his gestational age.

6- Lame for date, (Large for gestational age):• Infant with birth weight > 90`"

percentile of expected from his gestational age. 7- Low birth weight:

Any infant < 2.5 kg at birth (either premature 60 % or small for date 40 %) N.B. • VLBW < 1.5 kg. • Extremely LBW < 1 kg.

DEFINITIONSI PREMATURITY Definition: Premature (preterm) infant is an infant born at or before 37 w. gestation irrespective to his birth weight.

Aetiology: I- Idiopathic: The cause of prematurity is unknown in most cases.II- Maternal factors: 1- Low socio-economic class.2- Maternal age < 20 yrs and > 35 yrs.3- Maternal malnutrition during pregnancy.4- Maternal illness during pregnancy (PE, DM, TB, infections, cardiac diseases). 5- Maternaldrug abuse (e.g. cocaine).

III- Foetal factors:1- Multiple pregnancy.2- Congenital infections.3- Congenital malformations. 4-Hydrops foetalis.5- Foetal distress.

IV- Obstetric factors:1- Uterine malformations e.g. Bicornuate uterus. 2- Incompetent cervix.3- Placental premature separation (e.g.placenta previa). 4- Premature rupture of membrane. 5-Polyhydramnios.

;''s Features of preterm baby: 1- Measurements:

Birth weight: < 2.Skg (except infant of diabetic mother).

Birth length: < 47 cm (except infant of diabetic mother).

Head circumference: < 33cm. Chest circumference: < 30 cm.

2- Physical appearance: Scalp hair --) fine and wolly. Ear --) shapeless and soft (immature ear cartilage).

• Skin --4 pink, shiny, with low S.C. fat and covered - by lanugo hair.

i~i Breast nodule -~ < 3mm diameter (or even absent).E~ Nails --) Don't reach the finger tips. External genitalia --> Female (prominent

labia minoranot covered by labia majora)

~ Male (retracted or undescendedtestis)

Sole creases --4 Don't reach beyond the ant. 1/3 rd of sole

(or even absent).3- Physiological features:

Respiration: --~ Weak shallow with attacksof apnea due to:

Resp. center immaturity.Weak respiratory muscles. Pliable thoracic cage.

GIT: --4 Weak suckling, swallowing, digestionand absorption.Activity: --4 Weak crying & activity + hypotonia.

Body temperature: -~ Commonly subnormal andunstable due to immaturity

of heat regulating center andlow S.C. fat.

Physiological jaundice: -a Delayed (after

the 3`d day), prolonged (± 2w.) anddeeper (± 15 mg/dl).

~ Complications (Problems) of prematurity: 1- Respiratory:

RDS (HMD) -) (Discuss). Apnea-of prematurity ---~ (Discuss). More liable to pul. hge & pneumomthorax. More liable to congenital pneumonia. More liable to bronchopulmonary dysplasia (chronic lung disease).

2- CVS: PDA --> Heart failure. Hypotension (due to hypovolaemia ± cardiac dysfunction).

Bradycardia (due to apnea).3- CNS:ill Kernicterus (bilinibin encephalopathy) -4 (Discuss). More liable to ICH -> (Discuss).

Hypoxic-ischaemic encephalopathy ---> (Discuss),

4- Hematological: More liable to anaemia (Iron I & Folic acid

I). More susceptible to bleeding (Vit. K .L & DIC).

5- GIT: Prematurity is the most important factor for development of NEC -> (Discuss).

6- Renal:iii Immaturity of the kidney -41 capacity to concentrate urine --> more liability for acidosis or dehydration.

7- Immunological: • More susceptible to infection and sepsis due to deficiency of humoral and cellular response.

8- Nutritional: More liable to anaemia, rickets, PCM, hypoglycaemia andhypocalcaemia due to -4: • Weak suckling, swallowing, digestion and absorp.

High growth rate. Low reserve (e.g. small amount S.C. fat)

I Fe, Folic acid, Ca & P049- Retro-lental tibroplasia, (Retinopathy of prematurity)

41, Def.: Vasoproliferative retinal disorder which occurs mainly in premature

exposed to high 02 tension for long duration.

Risk factors: • T02 tension for long duration.Vit. E deficiency.

Pathogenesis: Passes through 4 stages Stage I --~ V.C. of retinal blood vessels.

Stage II --> V.D. of retinal blood vessels ± viterous hge.

Stage III ---> neovascularization of the retina.

Stage IV ---> traction on retinaby fibrous tissue --~

retinal detachment. Clinically: • No warning manifestations (so screening is needed)

Gradual development of astigmatism &retinal detachement.

Treatment: Mainly prophylacticLowest O, tension for the least duration is essential if 02 therapy for prematures is indicated.

Vit. E supply.•Any premature exposed to prolonged

02 therapy should be examined by ophthalmoscope at the age of one & three months. 10- Late sequalae of prematurity

Neurological: MR, spasticity, hearing or visual abnormalities.

Chest: bronchopulmonary dysplasia , cor-pulmonale.

GIT: Malnutrition, anemia, rickets, short bowel syndrome.Social: F'I'T, child abuse and neglect.

I SMALL FOR GESTATIONAL AGE I'lrEtiology:

A) Maternal causes:1. Placental anomalies. 2. Hypertension. 3.

Chronic heart or kidney disease. Theseconditions leads to changes in placental bloodvessels with resulting placental insufficiencyand intrauterine growth retardation.B) Fetal causes:1. Fetal infection. 2. Congenital

anomalies. 3. Twin pregnancy. A Clinical features:

The infant is active, alert, hungry with good cry & suckling (opposite to prematures)

The head is large in proportion to the body size.

Weight is low, length is normal and head circumference is normal.

Skin is loose, dry with scales.Subcutaneous fat is decreased.Trunk and extremities have less muscle bulk.Meconium staining of skin, , nails and umbilical cord.

~ Complications:1. Pulmonary problems: as asphyxia, meconium aspiration & pulmonary hge.2. Polycythemia.3. Hypoglycemia. 4. Hypothermia. 5. Hyocalcemia.6. Hyperbilirubinemia.

Management of Low Birth Weight(= of any high risk neonate)

I- Proper ante-natal care: Avoid maternal smoking, irradiation & drugs. Assessment of the foetus by ultrasound In special situation amniocentesis or foetal blood sampling may be indicated.

II-Immediate post-natal care:1- Place the baby under radiant warmer.2- Drying of the baby + suction of secretion. 3-Apgar scoring -~ ± Resuscitation if needed.4- Complete examination (see

examination of the newborn). 5-Care of the skin and asepticcutting of the umbilical cord. 6-Vit K1 (1 mg IM) is given for allneonates at birth.7- If the baby is large premature (> 2 kg) withno critical illness -~ discharge home.- If the baby is below 2 kg weight or has a

critical illness -~ incubator care.

III - Incubator care:

1- Temperature:Is adjusted to keep body temperature around normal (36.5-372 °C) -> so I heat loss & 1O, consumption.

2- Humidity:

Kept around 40-60% ---) so I heat loss, I water loss from bronchial tree (prevent dryness of the lungs).

3- O1_therapy:

For VLBW, RD, HIE, Apnea, Cyanosis, ~ Given in the lowest concentration for the shortest period.

• Excess 02 therapy in prematures may lead to retinopathy & chronic lung disease. 4- Prevention of infection:

All medical personelles must wash their hands before and after examining the baby

and no person with infection should be admitted into the nursery.

Antibiotic administration if indicated.

5- Feeding:

A- Oral feeding:

Type-4 • Better breast milk or premature artificial milk formula.

Routes--)* Suckling (In large prematures without respiratory distress).

Tube feeding through nasogastric tube (In neonates < 1.5 kg

or with mild RD) Frequency and amount -4

Begin with small amount --~ if no vomiting feeding every 2-3 hrs.

With stable condition increase the amount per feed gradually to

reach the daily needs (150 cal/k/day)

Vitamin and mineral supply -4V it. K ---> 1 mg IM => At birth.

Vit. A -4 3000 IU/dayVit. E ~ 15 IU/day => From 2"d weekFolic Acid -~ 1 mg/day.

• Vit. C. -4 50 mg/day. 1 1Vit. D -~ 1000 IU/k/day

•Fe -4 2 mg/k/day ~ From 2nd month

B- Intravenous fluids: Indications -Severe RD or intolerance tooral feeding.

• Amount -4 60-80 mUkg/day in ls` day of life with gradual T to reach 150 ml/k/d in the 5`h day.

Type --> • 1 S` day glucose 10%.

After that Glucose 10%: Saline (4:1) + Ca 1-2 mUkg/day added to the fluids

4 Duration --~ Maximum for 3-5 days, if oral feeding can't be reassumed total parenteral nutrition must becarried out (IV infusion of amino acids, fat, glucose, vitamins & minerals)

6- TTT of associations: Phototherapy for hyperbilirubinaemia.4 TTT of PDA (fluid restriction and indomethacin). TTT of infection (antibiotics).

7- Discharge from the incubator: Indications* Infant > 1800 grams with good suckling.

Maintain his temperature outside the incubator.

No critical illness.•Normal respiration (No

apnea, No RD, .......................) 4 Instructions to the parentsTo give vaccination according to dateof birth (not expected date)

To minimize handling and over crowding.

To maintain body temperature.

I POSTMATURITY Definition: Infant born after 42 week gestationirrespective to his birth weight.

• Aetiology: I- Unknown -~ most cases.2- T incidence with trisomies or anenccphaly.

Features: Face -~ opened eye and alert baby. Skin -~ wrinkled, dry with absent lanugo hair ± meconium staining.

Nails -~ long nails. Weight ---) Average or TT

Complications: Perinatal asphyxia ± Meconium aspiration * Polycythaemia.

Hypocalcaemia. * Hypoglycaemia.

q K- INFANT OF DIABETIC MOTHER

De f.: Neonate born to diabetic mother (true orgestational DM).

Commonly delivered preterm with T birth weight (Large for gestational age).

* Common problems:1- Polycythaemia: Due to ++ erythropiotin try to hyperinsulinism or foetal hypoxia (due to placental insufficiency)

2- Jaundice: Due to polycythaemia and 11 RBC's life span (try to glycosylated Hb). 3- Respiratory distress: RDS, TTN or cardiac causes.4- Convulsion:Due to: Hypoglycaemia =:> maternal hyperglycaemia ->

hyperplasia of islets cells of the foetal pancrease.After delivery and cutting of umbilical cord drop of foetal blood glucose aspancrease continue to secrete T insulin for some time.

• Hypocalcaemia =:> due to transient hypoparathyroidism & hyperphosphatemia.. 5- Cardiac problems: Cardiomegally & hypertrophic ventricular septum => HF. 6- Congenital anomalies =>

Renal anomalies GIT anomalies Cardiac anomalies. CNS anomalies (neural tube defect).

~ Imo: Causes of neonatal hypoglycaemia:1- Hyperinsulinism e.g. IDM, Rh incompatibility, P cell adenoma, Beckwith - Wiedmann syndrome.

2- 1 glycogen stores e.g. starvation, prematurity.3- Metabolic e.g. galactosemia, tyrosinemia & glycogen storage disease.

Causes of neonatal hypocalcaemia:1- Early onset (1" 3 days of life): IDM, prematurity & perinatal asphyxia.2- Latee onset: hypoparathyroidism, vit. D. deficiency, hyperphosphatemia, sepsis & shock.

"r Management: The same lines as any high risk neonate with ttt of specific complications: 1- Hypoglycaemia must be ttt by glucose 10% 2-4

mUkg IV followed by glucose10% maintenance infusion till

blood glucose return to normal. 2- Hypocalcaemia by Ca gluconate 10% 1-2 ml/kg IV. 3- Polycythaemia by partial exchange transfusion. 4- HF by inderal ((3 blocker)5- Jaundice by phototherapy.

k XI- THE UMBILICUS 1 4 Types of normal umbilicus (navel):

4 1. Normal navel: The skin of abdominal wall meets the umbilical cord at the level of the abdomen.

2. Amniotic navel: when the amniotic membrane of the umbilical cord covers the skin surface adjacent the base.

4 3. Skin navel: when the skin extends up the sides of the cord. ~N.B: The amniotic and skin navels arevariations of the normal.

Umbilical granuloma: 4 It is soft, vascular granulation tissue

present in the umbilicus and seen afterseparation of the cord. It is due to mildinfection of the umbilicus. The granulomaooze seropurulent discharge. ,

Treatment: cauterization by silver nitrate. If large, surgical removal.

4Umbilical polyp:*A rare anomaly resulting from persistence of all or part of the

omphalomesenteric duct or the urachus. The polyp is firm, bright red and hasmucoid secretion. It may be communicated with theileum or the urinarybladder leading to discharge of fecal material orurine.*Histologically, the polyp is formed of intestinal or urinary tract mucosa. *Treatment: surgical excision of the entire omphalomesenteric or urachalremnant.

4 Umbilical hernia:*Due to imperfect closure or weakness of theumbilical ring. It appears as a soft swellingcovered by skin that protrudes during crying,coughing or straining and be reduced easilythrough the fibrous ring at the umbilicus. Thehernia consists of omentum or portions of thesmall intestine.

*Treatment: Most hernias that appear before 6months disappear spontaneously by the age of1 year. Strangulation is rare and strappingis ineffective. Surgery is indicated if thehernia persists to the age of 3-5 years,causes symptoms, become strangulated orbecomes progressively larger after the age of2 years.

CHAPTER IX

HAEMATOLOEY

PHYSIOLOGICAL CONSIDERATIONS Haematopoiesis: It means production of RBC's which passes into3 stages:

1- Yolk sac haematopoiesis: Primitive RBC's during the first 8 weeks of gestation are formed in the wall of the yolk sac.

2- Visceral haematopoiesis: From the 2"a month of gestation up to the 6th month some haematopoiesis is present in the spleen, liver,kidney, thymus and lymph nodes.

3- Medullary haematopoiesis: From the 6th monthof gestation, the bone marrow becomes theonly site of haematopoiesis and persiststill adult life but active marrow (redmarrow) in adults will be restricted to skull,vertebrae, sternum & ribs.

Hemoglobin:

Hemoglobin is the unit of RBC's which carry oxygen, it's formed of haeme group (Iron) attached to 2 pairs of polypeptide chains (Protein).

0 Heme 0 Types of hemoglobin are changed according tothe polypeptide chains attached to the heme group:

I- Embryonic hemoglobins: They predominate in Embryo and disappear by the 3ra month of gestation, e.g. Portland and Gower Hb.

II-Fetal hemoglobin: (HbF) predominates during

the fetal life and gradually declines tillbecomes less than 2% at 6-12 months of age --->

HbF ((Xa 72).

III- Adult hemoglobins:Hb A 1 (major adult hemoglobin) -->a2(32

Hb A2 (minor adult hemoglobin) --> (X282So e During embryonic life -4 Embryonic hemoglobins

At the 2"a month fetal life -~ HbF predominateAt the 6`h month fetal life --4 HbF 90% & HbA 10%

At term -~ HbF 70°Io & Hb A 30%At 6-12 month postnatal -) HbF<2%, HbA2 2-3% & the remaining HbA.

Alteration of the hemoglobins by diseases: Hb A2--> • TT in B-thalassemia trait and megaloblastic anemia.

11 in a- thalassemia and Iron deficiency anemia.

4 HbF TT (>2%) in:Persons with homozygous B thalassemia.50% of person with heterozygous B thalassemia.

Hereditary persistence of fetal hemoglobin.

Some cases of sickle cell anemia.Diseases associated with hematological stress e.g leukaemia & pancytopenia.

~ Some Blood Indices:1- Hemoglobin level:

1" 2 weeks of life (16-20 gm %).• Infancy (10-14 gm %).v Adult (14 in female & 16 in male).

2- RBC's count:

6 million/CC in newborn. 4-5 million/CC after that.

3- Hematocrite value (Packed cell volume):The percentage of RBC's volume in 100 cc blood = 40-50.

4- Mean corpuscular volume (MCV): = Mean volume of single red blood cell

(Hematocrite value / RBC's count) x 10 = 75-90 femtolitre.

5- Mean corpuscular hemoglobin (MCH):= Amount of hemoglobin in single red blood cellMCH = (Hb /RBC's count) x 10 = 30 picogram

If low = hypochromic cells. If high = hyperchromic cells

6- Mean corpuscular hemoglobin concentration (MCHC):

= Concentration of hemoglobin in single redblood cell.

MCHC = (Hb/Ht value) x 100 = 33%7- WBC's count:• In newborn 10000 - 15000 / CC After that 5000

- 10000 / CC8- Platelet count:

150000 - 400000 / CC9- Reticulocytic count:

In newborn < 5% After that < 2%

If < 70 = Small RBC's If > 100 = Large RBC's

Microcytes. Macrocytes.

W:OlDfk It. , ' • Definition:

A condition in which the concentration of hemoglobin or the number of RBC's are reduced below normal values for age and sex.

Compensatory mechanisms: Before anemia becomes manifest and clinical presentation of reduced oxygen to the body organs occur, the body will respond to the hypoxia (reduced oxygen) by:

,P- If compensatory mechanisms fail to correct 102

manifestations of anemia occur: Symptoms: Anorexia, loss of weight, restlessness and easy fatigability.

• Later on headache, fainting, anginal pain and intermittent claudications. Signs:

Pallor (the most important sign). Hemic murmers (functional, systolic), tachycardia & anemic HF in severe cases.

Aetiological classification of anemia Decrease production Blood loss

u= Acute or chronic bleeding.

Increase destructionu

= Causes of hemolytic anemia1- Decrease number of RBC's precursors in the bone marrow.

u• Pure red cell anemia (Congenital & acquired)• Bone marrow infiltration (Leukaemia, lymphoma myelofibrosis)

Aplastic anemia

u2- Decrease production despite normal RBC's precursors in bone marrow.

u Anemia of chronic

infection and inflammation. Anemia of chronic renaldiseases

3- Deficiency of specific factors required for RBC's production.

1- Microcytic hypochromic anemia 2- Macrocytic anemia. 3- Normocytic anemia.

Iron deficiency (Microcytic)

• Folic acid and B 12 deficiency (macrocytic)

Protein or copper deficiency (Normocytic)

A- Anemia resulting from.~.~ RBC's precursors in bone marrow

I- Pure red cell anemia:(hypoplastic anemia)The precursors of RBC's only in thebone marrow are decreased or absent:

1- Congenital pure red cell anemia (Diamond Blackfan S.)

familial disease of unknown cause chch by anemia, and associated

congenital anomalies e.g. triphalangial thumb.

Lab: I RBC's, normal plateletsand WBC's

TTT: corticosteroids -~ If no response repeated blood transfusion.

2- Acquired pure red cell anemia:i - Immune disease against RBC's precursors.ii - Idiosyncrasyto chloramphenicol iii- Infection with Parvovirusiv - Idiopathic (Transient erythroblastopenia of childhood).

II. Bone marrow infiltration:Leukaemia, Myelofibrosis or lymphoma may invade the bone marrowand replace the stem cells resulting in:

11 RBC's precursors -4 hypoplastic anemia

or 11 Megakaryocytes -4 thrombocytopeniaor .iJ. WBC's precursors ---) leukopeniaor 11 All elements of blood =

pancytopenia Def. Absence or deficiency of the3 elements of Bone marrow.

• Causes: a Congenital: 1- Fanconi anemia.

2- Familial aplastic anemia.

III- Aplastic anemia:~Acpuired:

1- Idiopathic (70%): Unknown cause2- Secondary (30%): Chemicals: insecticides, war gases. Viruses: e.g. Hepatitis, CMV & EBV. Irradiation. Drugs:

Antineoplastic Antibiotics Anticonvulsants Anti-inflammatory Antimalarial Antithyroid

--~ Endoxan, methotrexate, 6MP.-~ Sulpha, nitrofurantion, chloramphenicol. --~ Hydantoin, carbamazepine --~ Indomethacin, phenylbutazon. --~ Chloroquine--~ Carbimazol, propylthiouracil.

Clinical picture:1- Anemia: Pallor & other manifestations of anemia. 2- Leukopenia: Recurrent infection

3- Thrombocvtopenia: Purpura, bleeding4- No or2anomec. , alY (liver, spleen, LN)5- Features of the cause:

Fanconi anemia (AR) is chch by: Variable onset of anemia (4-12 yrs old) Skin pigmentation, short stature, skeletalanomalies ( abnormal thumb, absent radius, skull anomalies, ....).

MR in 20 % of cases.P History of drug, irradiation or chemical

exposure in try aplastic anemia.

~ Investigations:Blood --> Pancytopenia (Also ~ reticulocytes) + macrocytic RBC's. Bone Marrow -a hypocellularity of a113 elementsIn Fanconi ~ T chromosomal breakage (>20- 70%)

*D.D.- Other causes of pancytopenia: • Hypersplenism

Bone Marrow infiltration•Megaloblastic anemia

- Other causes of macrocytic anemia: see laterA Treatment:1- Supportive care:

TTT of anemia (packed RBC's transfusion ifHb < 7 gm / dl).

TTT of bleeding (avoid IM injection / fresh frozen plasma).

TTT of infection (antibiotics / isolation / G-CSF).

2- Specific ttt:Immunosuppressives (corticosteroids, cyclosporin A & antithymocyte globulin).

Androgens.

Splenectomy. IV gamma globulins• Bone marrow transplantation

I B- Iron deficiency anemia IIron metabolism:Most of dietary iron is present in ferricstate, which is released & changed toferrous state by the combined action of HCLand Vit. C. then absorption occurs from theproximal small intestine (about 10% ofdietary iron is absorbed only).The absorbed iron is carried on plasma proteincalled transferrin, the transferrin can carry3 times than average of plasma iron whenit's said to be fully saturated. So, TIBC(Total iron binding capacity) = 300-400ug/dl.

• Normal serum iron is 60-120 ug/dl:• Daily requirements of iron is about 1 mg daily & as 10% only of dietary iron is absorbed so the daily diet must contain 10mgiron Functions of iron:

• Formation of hemoglobin in RBC's•Essential in certain enzymes necessary for

body functions as catalase, MAO, ... S-zAetiology:1- 1 Intake: Exclusive breast feeding or

unfortified powdered milk withoutsupplementation is important cause ofanemia at 6-9 months of age (afterexhaustion of transplacental iron stores)

2- 1 Absorption:, in malabsorption or excess intake of tea, antacids, ........... 3- Chronic blood loss:

Ankylostoma duodenale

Cow's milk protein allergy Peptic ulcer, piles, Meckel's diverticulum,...

Frequent blood sampling in neonates4- Increase demands: e.g.

prematures & adolescents `!r Clinical Manifestations:

1- General manifestations of anemia.2- Manifestations of enzymes deficiency (Defective alertness, learning & concentration) 3- Other manifestations

* Investigations: 1. Hypochromic Microcytic Anemia

I I IMCH<30 Pg MCV< 70 Fl Hbl,

RBC's~ 2. Serum iron 11 (N. 60-120µg/dl) 3. TIBC TT (N. 300-400 µg/dl) 4. Serum ferretin 11 (reflecting iron stores) 5. Transferrin receptors TT. 6. For the cause e.g. stool analysis for ankylostma.

*Differential diagnosis:Causes of Hypochromic microcytic anemia:

Cause Serum Fe TIBC Other investigation

N.B1. Ironi anemia

11 TT - Stool for occult

The commonest cause

2. Anemia of

- For the cause

Usually normocytic,occasionally hypochromic3.

Sideroblastic

Normalor TT

Normalor 11

- Siderablastsin blood

Abnormality in haernemetabolism either Gong. or4.Lead

poisoningNormal Normal - Basophilic

stipplingof RBC's & T

lead

History of exposure to lead

5. (3-Thalassemia

Normalor TT

Normalor 11

- Reticulocytosis- T HbA,

(Hemolytic microcytic

N.B. cr- Mentzer index = MCV RBC's count (If < 13 -a

(3 - thalassemia trait, if > 13 -4 Fe .~) ~r

Treatment of iron deficiency anemia:

1. Prophylactic: Oral iron preparations are given after the 3`d month (2mg/kg/day)2- Treatment:a- Causal treatment (e.g. Ankylostoma, Mickel's, ...).c. Blood transfusion: In severe cases or anaemic H.F.

N.B. amoral iron preparations: -ferrous sulphate(20 % elemental Fe)-ferrous lactate(19 % elemental Fe)-ferrous gluconate(12 % elementalFe)

3- Criteria of improvement:a- T appetite and .(- irritability (within one day) b- T reticulocytic count (within one week) c- T Hb to normal values (within one month).

b- • Oral iron preparations (6mg/kg/day) Parenteral iron in severe vomiting Iron rich foods

For 4-6 weeks after return of indicesto normal (to fill iron stores).

C- Megaloblas tic Anemia JPathogenesis of megaloblastic anemia:

Megaloblastic is a term denoting abnormalcell production in which IDNA formationoccurs with normal RNA, as a result thenucleus becomes smaller in relation tolarge cytoplasm (Nucleo- CytoplasmicDissociation)

:• Megaloblastic anemia is anemia resultingfrom folic acid or vit. B 12 deficiencywhich are essential substances for DNAproduction resulting in megaloblasticchanges not only in RBC's but WBC's andPlatelets may be also affected:

RBC's1- Folic acid I or B 12 1 => Megaloblastic cells in bone marrow

wsc'sPlatelets

Anemia r2- Megaloblasts are destructed in marrow (ineffective cytopoiesis) -- Thrombocytopenia ±

_J-eukopcniu ±

Metabolism of Vit. B12

Folic acidSources: Animal origin

*-Animal (liver, seafood, Liver)Requirements: 5-20 µg/day. b 20-60 µg/day.

Body Store are much Body stores B12 b Histidine--> Form]

minoglutamicacid (FIGLU) - Folic

Function,: Methyl malonic succenyl CoAAbsorption: Stomach b Rapidly absorbed from

proximaljejunum

release Intrinsic factor (IF)which bind to B12

-~ Aetiology of Vit. B12 & folic acid deficiency:

Causes of Vit. B1211

Causes of Folic acid.~.~1- .Intake: `•Very rare except

breastfeeders of

~` Not Common:1-Goat milk2-Excess heated milk2- 1

Absorption1-Generalized inalabsorption2-IF pernicious anemia

1- Generalized malabsorption2- 1 folic acid absorption by drugs

3- Others Defective Increase requirements:- Prematurity (Stores)

- "Transcobalmine II deficiency

• Clinical manifestations:1- General picture of anemia2- GIT manifestations esp. with folic acid" (redglazed tongue, abd. pain, colic,...)3- CNS manifestations only with severe B12 44

(Subacute combined degeneration) Posterior column degeneration

Peripheral nerve degeneration

Pyramidal tract lesion Investigations: 1- For anemia I RBC' s & .L Hb

2- For me2aloblastic anemia: CBC : - Macrocytic anemia (T MCV > 95 fl

& T or normal MCH) - + Leukopenia& Thrombocytopenia.

Bone Marrow:- Megaloblastic changes• Blood chemistry: -T serum LDH,

muramidase and iron 3- For the cause:

Folic acid deficiency:i- Low serum folate (<5 ng/ml)

ii-FIGhU Test: Excess FIGLU secretionin urine after an oral dose of histidine

• B12 deficiency:i- Low serum B 12 (<100 Pg/ml)ii- Methyl malonic acid: excess secretion in urineii- Schilling test: IM large dose of non radioactive B12 (1000 µg.) to fill B12

stores, followed by oral small dose (2µg) of radioactive B12.Normally 10-30% of the radioactive B 12 will be excreted in urine.- In case of megaloblastic anemia due to ~B 12 absorption < 2% will be excreted. - If the excretion is TT by IF addition, IF deficiency will be the cause.

Differential diagnosis:

Other causes of macrocytic anemia:1- Megaloblastic anemia (B 12 & folic acid ~ / Lesch Nyhan / orotic aciduria) 2- B.M. failure (aplastic or hypoplastic anemias) 3-B.M. infiltration (leukemia, myelofibrosis).

4- B.M. response to hemolysis or hge.5- Others (Cretinism / Down syndrome / liver disease)

Treatment:

1- Treatment of the cause2- In cases of vit. B12 deficiency:

• If Associated with neurological manifestations 1000 µg IM daily for at least 2weeks then maintenance therapy 1000 µg IM/month for lifeIf not associated with neurological

manifestation 1000 µg B 12 IM/month for life. 3- In cases of folic acid deficiency:

Initially low dose of folic acid 50 µg/day isgiven, as large doses may worsen the neurological conditions in cases of B 12 deficiency.

:• If the response to ttt occurs (THb% & Reticulocytosis), the full dose of folic acidis given (5 mg/day/oral) for at least one month.

D- Hemolytic Anemia I • Anemia resulting from increase destructionof RBC'sNormal bone marrow can increase its output ofRBC's production up to 7 folds during stress,so manifestations of hemolysis do not occuruntil severe reduction of RBC's life spanoccurs. Activation of the extramedullaryhematopoietic tissues especially in theabdominal viscera may also occur

C- Causes:

1A- Membrane defect- Heridetary spherocytosis - Heridetaryelliptocytosis - Paroxysemal nocturnalhemoglobinuria

I. Intracorpuscular defects

B- Hb defect1-Synthetic defect (Ouantit.) - a thalassaemia- (3 thalassaemia 2-Abnormal Hb: (Qualitat)-Sickle cell anemia- Hb SC disease

II- Extracorpuscular defects

Immune mechanism Non immune mechanism

Passively acquiredAntibodies (isoimmune) "Hemolytic disease of the newborn" -RH incomp. -ABO incomp -Minor group incomp.

Active antibody formation (autoimmune) -lry autoimmunehemolytic anemia - try autoimmunehemolytic anemia- Infective agents e.g. gram -ve septicaemia- Physical agents (microangiopathic hemolytic anemia): renal vein thrombosis, hemolytic uraemic syndrome & DIC

- Chemical agents e.g. heavy metals, drugs.- Hypersplenism- Wilson disease

N.B. Hemolytic anemia can be also classified into:

1- Acute hemolytic anemia e.g. G6PD deficiencyMost of extracorpuscular defects.Hemolytic crises of chronic hemolytic anemia

2- Chronic hemolytic anemia e.g. thalassaemia and sickle cell anemia.

C• Manifestations of hemolytic anemia:1- Manifestations of anemia: See before2- Manifestations of hemolysis:

I- Chronic hemolytic anemia Tinge of jaundice: due to excess bilirubin from Hb destruction.

Hepatosplenomegaly: (due to extramdullary hematopoiesis to compensate forhemolysis and iron deposition in RES).

Gall stones: pigmented gall stones develop on long-standing hemolysis (formed of calcium bilirubinate)Characteristic skeletal manifestations: hyperplasia of the erythropoietic marrowleads to expansion of the medullary spaces in the skull & hands: Skull large, prominent maxillae, protrudedupper central incisors

(Mongoloid face) Hands => Broad & light

Hematological crises•• Aplastic crises =:> Transient attacks of bone marrow failure occurs in

patients with chronic hemolytic anemia especially when exposed to infection as Parvovirus B 19, manifested by Tpallor without jaundice.

Megaloblastic crises => folic acid

deficiency on top of chronic hemolysis Hemolytic crises => Precipitated by infection manifested by Tpallor & jaundice + dark urine (hemoglobinuria).

II- Acute hemolytic anemiaAcute attacks of : pallor, jaundice, dark urine

(hemoglobinuria) ± fever3- M • anifestations of the cause: See later

C• Investigations of hemolytic anemia: 1-Investigations for anemia:

• Low hemoglobin Low RBC's count (than normalvalues for age, sex).

2- Investigations for hemolysis: Indirect evidence of hemolysis:1- Reticulocytosis in peripheral blood.2- Blood chemistry:

T unconjugated bilirubin & serum iron I plasma haptoglobin & hemopexin

3- Radiological signs (in chronic hemolysis):

Gall stones can be detected by X-ray or ultrasound

Skull X-ray shows: macrocephaly, widening of the diploic space with hairon end appearance.

Hand X-ray shows rarefaction (I density) Direct evidence of hemolysis: 1-Presence of hemoglobin in urine (hemoglobinuria) ~ in acute hemolysis 2-Estimation of RBC's survival by isotope techniques e.g. sodium chromate.

3- Investigations for the cause: See later.

HERIDETARY SPHEROCYTOSIS Aetiology: Autosomal dominant disease (no family history in 25 % of cases) characterized by abnormal RBC's membrane.

Pathogenesis: Abnormality in cell membrane lipoprotein (spectrin) --~ TNa+ permeability intothe cell -~TATPase activity & glucose consumption at the membrane to get the excess Na+ outside the RBC's ~ Premature aging of RBC'sT Na' influx-->Twater content inside the cells ~ swelling of RBC's which becomes early destructed especially in sinusoids of the spleen.

Clinical manifestations: As any case of chronic hemolytic anemia with:1- Onset may be during neonatal period leading to neonatal anemia & jaundice. 2- Pigmented gall stones are commoner than othercauses of hemolytic anemiaespecially during late childhood.

Investigations:

As any case of chronic hemolytic anemia. Investigations for spherocytosis: 1- Peripheral blood -->spherocytes (small rounded RBC's

with loss of its central pallor) 2- Osmotic fragility test -~

Idea: When RBC's are placed in hypotonic solution they imbibe water and become

swollen. As hypotonicity of the solution increased the rate of water flow insidethe RBC's Mill rupture of RBC's occurs.

Normally: The rupture: * Begins at 1/2 tonic solution (0.45% saline)

* Completed at 1/3 tonic solution (0.3% saline)

In spherocytosis: The cells are already swollen so osmotic fragility is increased.

The rupture: * Begins at 3/4 tonic solution (0.75% saline)

* Completed at 1/2 tonic solution (0.45% saline)

3- Auto hemolysis test -->If RBC's are incubated for 2 days at 37 C° -4Normally -4 <5% of RBC's are hemolysed.In spherocytosis--4l5-30% of RBC's are hemolysed ( as spherocytes are

deficient in glucose support, so -4 if glucoseis added ->Ihemolysis)

Treatment: 1- Blood or RBC's transfusion, if anemia is severe and during crises.2- Splenectomy: Cure the patients by

preventing hemolysis & crises but not correct the morphology of RBC's.

Precautions: 1- Not done before 5 years old toprevent salmonella osteomyelitis

H.influenza and meningoccal or pneumococcal infections.

2- Vaccination against pneumococci & H.influenza before operation.

3- Prophylactic penicillin after operation tilladult life.

GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY

"favism"

C Aetiology:XR disorder (male > female) due to deficiency of G6PD enzyme in RBC's.

C• Pathogenesis: G6PD is the enzyme necessary in HMP shunt which result in formation of reduced glutathion that protects the RBC's against oxidizing agents.

In G6PD deficiency, Glutathion is oxidized --> exposure to oxidizing agent lead to precipitation of hemoglobin on the inner side of RBC's membrane (Heinz bodies) and their destruction.

Oxidizing agents include: 1- Food: especially fava beans. '2- Infections: pyogenic or viral infections.3- Drugs:Antimalarial --> Quinine & quinidine

Antipyretics -~ Salicylates.Antituberculous -> INH & paraaminosalicylic acid

Antimicrobials -) Sulpha & ChloramphenicolC* Clinical manifestations:Manifestations of hemolysis as before develop in 3 forms:1- Acute hemolysis -4 Rapid deterioration occurs12-24 hours after ingestion or

contact with the oxidizing agent in the form of acute pallor,jaundice &

dark urine ± fever. 2- Neonatal anemia & jaundice3- Chronic hemolysis --> Rare

C* Investigations: General investigations for hemolysis

During the attack Heinz bodies appear in RBC's (Blood film)

1-2 months after the attack enzymatic assay of G6PD reveals low amount of theenzyme in blood (not measured during the acute attack as RBC's with lowenzyme level will be destructed).

C*Treatment:41~ Prophylactic:1- Identification of the patients who are given cards referred to their disease(G6PD I patients)

2- Avoid foods & drugs which predispose tohemolysis in known G6PD I patients.

3- In febrile child with G6PD I paracetamol or ibuprofen is given (safe)

Curative: (during the attack)1- Stop intake of any oxidizing agent.2- Packed RBC's transfusion (5-lOml/kg)& may be repeated in severe hemolysis

C- Prognosis: The disease tends to improve with age. Spontaneous recovery from hemolytic crises isthe normal outcome

THALASSAEMIASAR disorders characterized by defective globin synthesis (.production of one globin chain)~ Defective a chain production --) a thalassacmia (4 genes are responsible for (x chain formation) so, if:~ 4 genes affected ~ Still birth

-~ 3 genes affected ~ HbH disease (severe)~ 2 genes affected ~ a thalassaemia trait ( Mild) -~ 1 gene affected ~ Silent carrier

~ Defective a chain production, -4 P thalassaemia (2 genes are responsible for R chain formation so if:-> 2 genes affected -4 ~3 Thalassaemia Major. --~ I gene affected -+ ~i Thalassaemia. Minor

(P-Thalassaemia major: (Cooley's anemia)The most common cause of ch. hemolytic anemia in Egypt & Mediterranean areas.

C- Pathogenesis:Q - chain production Leading to

t

lDeposition of excess a I production of HbAi ((Xz 02)chain inside the RBC's

and compensatory production of

--~ hemolysis other Hbcontaining non Beta

chains esp.Hb F((XzY2)

l

lAnemia T Level ofHbF (TOZ affinity)

Tissue hypoxial

Compensatory TRBC's production

___________i_

l lMedullary hematopoieses

Extramedullary hematopoieses1 l

Bone marrow expansion

Hepatosplenomegaly(Skeletal changes) ± hypersplenism

2- Iron TTsecondarv to: CompensatoryT intestinalabsorption of iron. Repeated blood transfusion.

• Hemolysis of RBC's* (T serum iron -~ Deposition of iron in various organs = hemosiderosis)

C C/P:I - Manifestations of anemia ( see before)2- Manifestations of chronic hemolytic anemia. (see before) 3- Specific features of thalassaemia:Age must be above 6 months old (when P chain

becomes predominant). Mongoloid features & HSM ate typical esp. long standing cases

Hemosidrin (iron deposition) Skin --~ Bronzed colour Liver & spleen ---> HSM Pancrease --> DM Heart -> Cardiamyopathy Pituitary --> Hypopituitarism, hypothyroidism, hypoparathyroidism.

Gonads ->Hypogonadism. Investigations: 1- Investigations for anemia.2- Investigations for hemolysis.3- Specific investigations for (3-Thalassaemia major: v Blood film: - Microcytic hypochromic anemia

- Target cells (centrally nucleated Hb)

Hb electrophoresis: I HbA & T HbF (all cases) & T HbA2

Genetic counseling: Premarital for high risk families

Complications & causes of death: 1- Frequent blood transfusion:

Febrile reaction4 Allergic reaction4 Disease transmission (Hepatitis, AIDS, $,........) 4 Incompatible blood transfusion

2-Failure of the heart:Anaemic heart failure if no blood transfusion is given, while excess transfusion may T load on the heart due to hypervolaemia. 3- Growth retardation.4- Hvpersplenism: with resultant pancytopenia. 5- Hemosiderosis: see before

Management: 1- Regular Packed RBC's transfusion:

10-15 ml/kg every 4-6 weeks is sufficient to keep Hb level above lOgm/dl.Frequent transfusion will keep Hb level above 12 gm/dl (super transfusion).

Regular blood transfusion will permit normal growth, .~ organomegaly andminimize skeletal changes

Recently ncocyte transfusions have been shown to be more effective as those RBC's survive longer.

2- Iron chelating agents: Deferroxamine (Desferal):40 - 60 mg / kg / day IM, [.V. or better continuousS C. pump for 12 hours/day -~ 4-5 days/week (side effects: local reaction,fever, myalgia, increase risk of yersinea infection).

Other oral agents under trials as - deferiprone.-ICL670 (50 - 75 mg / kg / day).

3- Dietary support: Good caloric intake with suitable ratios of food elements.

Folic acid supply (1 mg/day) oral to preventmegaloblastic crises, as folic aciddeficiency is common in 0-thalassaemia due tohyperactive bone marrow withdepletion of folate stores in new RBC's synthesis.

Iron is contraindicated.

4- Treatment of crises: Blood transfusion ± treatment of infection.

5- Splenectomy: Indicated in

huge spleen causing severe pressure symptoms

hypersplenism --) indicated by increase theamount of transfusion than usual (> 250 ml / kg / year) or appearance of pancytopenia.

• Precautions:See spherocytosis

6- Bone marrow transplantation:~ Curative but difficult, expensive and must be

performed early (before excess transfusion as this may lead to more liability for graftrejection).

7- Gene therapy: --> under trialC* Prognosis:Most of the patients die from complications between 20-30 yrs old

I____________________________ P-Thalassaemia

minor: -~ Heterozygous forma Most of the patients have no or very mild symptoms. Accidental appearance of microcytic anemia in CBC is the usual finding and it must be D. D. from Iron deficiency anemia.

Diagnosis: * T HbF (only present in 50% of cases) * T Hb A2 (diagnostic)

(Hereditary persistence of foetal Hb: HPFH IA condition associated with presence of HbFinstead of HbA which is normally distributedin RBC's with no excess a chine so very mildanemia is present + Good prognosis.

SICKLE CELL HEMOGLOBINOPATHY0 Autosomal recessive disorder characterized by

qualitative defect in globin synthesisin which substitution of amino acid number 6(glutamic acid) in R-chain by valine occurs,leading to formation of abnormal hemoglobin(HbS) -) which can't withstand hypoxia

Pathogenesis:

Exposure to hypoxia -~ lib istortion and abnormal shape of RBC's (Sickling)

These abnormal cells aggregate, leading to vascular obstruction and early destructed (hemolysed RBCs) by the R. E. S.

2 forms are present: Homozygous form ~ sickle cell anemia Heterozygous form -~ sickle cell trait

I Sickle cell anemia: ---) Homozygous form (SS) Clinical manifestations:

~= Manifestations of anemia. "see before"v Manifestations of chronic hemolysis. "see before" =~ Specific manifestations of sickle cell anemia:

1- Presentation after 6 months oldCommon in Negroes.

2- Let ulcers are common.3- Renal impairment is common (even nephritis & haematuria).4- Splenomegaly initially is followed by shrinkage as a result of repeated splenic

infarctions (autosplenectomy) This defectivespleen may be associated withinfections (see hyposplenism).

5- The same crises as usual, but other crises mayoccur in sickle cell anemia:

~O- Vaso-occlusive crises: The most frequent, precipitated by hypoxia (anaesthesia,

pneumonia, shock,....) Hand foot syndromes infarction in small bones of extremities (symmetrical

bone pain & swellings) Pulmonary infarction -4 chest pain, hemoptysis (sickle chest syndrome).

Stroke -4 Due to cerebral artery occlusion. Hematuria Due to renal infarction. Autosplenectomy.

Sequestration crises: precipitated by dehydration; occurs in patients < 2 years. Sudden pooling ofthe blood in the spleen-) shock, massive splenomegaly.

Hyperhemolytic crises: Due to associated G6PD1.

Investigations:

1- Investigations for anemia.2- InvcstiRations for hemolysis3- Special investigations for sickle cell anemia: *Sickle cell in peripheralblood, if not detectedsickling can be enhanced by adding Na metabisulfite.

* Hb electrophoresis -4 showes HbS (90%) and HbF (2-10%)

U Treatment:E~ The same lines for thalassaemia except splenectomy:4 Treatment of crises:+ Analgesics & good hydration for vaso- occlusive 4, Blood transfusion for hemolytic & aplastic crises+Antishock measures, blood & even emergency splenectomy arc indicated insequestration crises

W Treatment of autosplenectomy: (Vaccination + penicillin -~ see spherocytosis)

Sickle cell trait: -~ heterozygous form (AS) I The patient's blood contains mixture of (HBS) and (HBA)

Normally asymptomatic but severe hypoxia may lead to crises

Patients are resistant to falciparum malaria.