Disease of Infancy and Childhood

Diseases of infancy and childhood

Terminology -Neonatal peroid: first 4 wks. Early: first 7 days,Late: after 7 days

-Infancy : 1 yr. -Early childhood: 1-4 yr. -Late childhood : 5-14 yr. -Newborn : 24 hr. -Perinatal death = neonatal death+fetal death

Body weight and gestational age

• Preterm : 37 wk.• Posterm : 42 wk.• AGA: BW ( 10-90 Percentile )

• SGA: BW ( < 10 Percentile )

• LGA: BW ( > 90 Percentile )

CAUSE OF DEATH

Intrauterine growth retardation (IUGR)

Etiology : Unknown : Fetal – Chomosome abn ( tripoid, trisomy 18,17, 21, other ) , congenital anomaly,TORCH

: Placenta –UVP anomaly, mosacism(genemutate in zygote:trisomy 7 )

: Maternal –Vascular( HT), narcotic, ALG,smoking, drug, malnutrition.

Immaturity of organs

Lung : (26-32 wk) alveolar epi. type I– II respiratory distress syndrome ( RDS )Kidney : premature glomeruliBrain : No gyri, sulci --- def. of myelin – eff. control temp.Liver : Extra med. ----transcient phy. jaundice

APGAR SCORE

Method for evaluate phy. condition --- survival

Score at 5 min (0-1) ---- death 50% 4 ---- death 20% >7 ---- death 0 %

Evaluation of new born

Stillbirth

• No sign of life(> 20 wk)• DFIU,intrpartum death (DR= 0.55-

1.93LA)• Etiology :chr.abn, IUGR,maternal,

perinatal infection, immuno dis., intrapartum hem, postterm

Birth injuried :

Clavicle Fx ,facial N , brachial plex ,intraclanial inj.humural Fx.

Birth injuries of head 1.Intracranial hemorrhage :most common important birth injury -excessive mold skull --- subdural,subarachnoid. intraventricle hem. ---- ICP --- brain herniation ---- vital med. center

2. Caput succedaneum ---- fluid in soft tiss. of scalp ,Cephalhematoma ---- subperiosteum hem. of scalp , 25% skull fracture

Definitions

• Malformations; morpho. def of organs---

result abn. develop Dysplasia; abn. organized cells in tissue

Deformations; abn form ,shape, position of body by mechanic.

Disruptions; defect of organs by ext. breakdown

Sequences: pattern anomaly from single known

Cause of con genital mal

Definitions (continues)

• Syndrome: multiple anomalies,not

representing sequence from single agent( viral or chromosome abnormal )

Association: non random occur in several

defect ,not seqeunces and syndrome

Descriptive terms

• Agenesis: complete absence of organ

• Aplasia: absence of organ due to failure del.

• Atresia: absence of opening hallow visceral organ

• Hypoplasia: under del. of organ, decrease No. cells

• Hyperplasia: over del. of organ, increase No. cells

• Hypotrophy: decrease in size of cells

• Hypertrophy: increase in size of cells.

Descriptive terms (continue)

• Dysraphic: failure to fuse: e.g. spinal bifida

• Involutional failure: persist emb.stru. e.g. thyroglossal duct cyst

• Division failure: incomplete cleave tissue e.g. syndactyly

• Ectopia or heterotopia; organ outside normal site

• Dystopia: retention of organ at site during development

Figure 11-7

Cause of malformations

Genetic cause: karyotypic aberration( 10-15 %) birth

life e.g. trisomy 21. Klinefelter syn , Turner syn, trisomy 13 (Patau syndrome) : single gene mutation e.g. polydactyly :mutlifactorial inheritance

Environmental cause: viruses :esp rubella, CMV

: drugs and chemical e.g. alcohol : radiation

Multifactorial causes

Mechanism of malformations

Timing perinatal mal: -Embryonic period (organogenesis) 9 wk.

-Early in 3 wk may normal or abortion -Between third and ninth wk (4-5 wk) -Fetal period :growth and maturation of organ

Teratogens: -effect cell pro.,migration and differentiation

e.g.anticonvulsant drug --- dediff. mesenchymal tissue –

cleft palate

Morphogenic gene: Hox gene

Perinatal infection Transcervical(ascending) infection -bacteria, virus ( herpes simplex II )— Intrauterine

pneumnia,sepsis,meningitis.

Transplacenta(hematologic) infection - Virus: e.g. TORCH : hepatosplenomegaly,

hem.anemia,pneumonia, myocarditis, vesicular skin : MD, cataract, CHD, bone defect

: Parvovirus B 19 : replication in RBC (intra nuclear

inclusion) ---- abortion, stillbirth, HF.

-Bacteria : Group B strep: most common early sepsis :most common bact. meningitis

: Listeria and candida : late sepsis

parvovirus

Respiratory distress

• HMD , sedation , brain inj , AFA , IUA

• HMD: preterm ,term with DM , C/S : 30 min after birth ---tachypnea --

cyanosis --- ground glass x-ray

: 60% less than 28 wk, 15-20% 32-36 wk.Gross: Airless+ solidMicro: atelectasis+ overdistend alveoli+pink

membrane on air spaceSequelae : RLFP,fibrosis BPD , IVH, NEC

Fig11-10

Meconium aspiration syndrome (MAS)

-Asphyxia --- abn. rep.motion---amniotic fluid

in air space- Micro: meconium( desquamate squamous

cells,bile pigment, lanugo hair)

Hydrop fetalis

subcutaneous edema+ effusion in

pericardial,peritoneum, pleural cavity. -Mech: anemia + decrease protein---

decrease intravacular pressure ----- leak of fluid

-Cause : immune ---erythroblastosis fetalis : nonimmune > 90%

Fig 11-12

Table 11-5

Inborn errors of metabolism

- Phenylketonuria : homozygote AR --- lack

phenylalanine hydroxylase – PKU--- mental retard- Galactosemia : homozygote AR --- lack of

galactokinase---- galactitol -----MD, cataract, hepatosplenomegaly, failure to thrive, diarrhea

- Cystic fibrosis: defect Cl transport in epithelium

cells by cystic fibrosis gene (chr 7) --- exocrine in respiratory, GI tract, reproductive organ

: poor weight gain, malabsorption,

pulmonary problem

Sudden infant death syndrome(SIDS)

90% SIDS less than 6 m,unexplained by autopsy,

heterogeneous entity,sleep at night ,healthy Micro: anoxic change : VH, gliosis,

pulmonary congestion , petechial hem. at pleura etc.

Neoplasm most benign, 2% malignant

Hemangioma :most common tumors in infancy

:skin, face,scalp Gross: red blue mass Micro: numerous vessels with unremarked endothelium : Spontaneous regress :asso hereditary e.g. von Hippel-Lindau dis.

Lymphangioma : skin ,neck,axilla,mediastenal,retro.

:micro :lymph vessels in cyst or space :increase in size after birth

Teratoma : 2 yr or adolescence,sacrococcygeal

Gonad,medias, retroperitoneum,head neckSacrococcygeal teratoma : 1:20000-40000 : M/F=4:1

-10% asso congen.def hind gut,mid line defects - Gross: cystic mass with mature tissue - Micro : meso,endo and ectoderm. - 75% mature contains mature tissue -12% immature contains mature and immature tissue - 12.5 % mixed germ cell tumor

Malignant tumor in infancy

abn.del and tumor inductionfamilial or genetic aberrations : regress spon. or cytodiff. , improve survival and cure.

Common : hemato malignancy. , nervous system, soft tissue,bone, kidney.

Neuroblastoma Vs ganglioneuroma

Most common childhood solid mal. tumorMost common diag. less than 1 yr.Location: 25-35% adr. med ,symp chain

(paravertebralpost.mediastinum or lower abdomen)Gross: minute nodule to huge massMicro: small blue round cells with neurofibrillary(Homer-Wright) diff. to ganglia cells(psuedorosettes)--- ganglioneuroma , ganglioneuroblastomamet to blood stream --- liver, lung, bone

Clinical staging

• Stage 1 : confined in organ origin• Stage 2: extened beyond organ, not cross mid

line• Stage 3: beyond midline• Stage 4: metastasis to viscera, distal LN, soft

tiss.. skeleton Stage 5s (special) :small adr. tumor to liver,skin, bone marrow without bony destruction

Clinical course

Most < 2 yr , fever , abdominal mass,weight loss, proptosis

Prognosis ; < 1 yr--- excellent prognosis (no related stage)

< 1 yr.stage 1,2 ---- 95-98 % 5 yr. survival Stage 5 s ---- 80% 5 yr. survival Chromsome 1 deletion ---- worse prognosis 25-50% asso deletion of q chr.14 ---

agg.behavior

Groups of prognosis

First gr : < 1 yr, hyperploid, high Trk A, no n myc

oncogene,adsence of deletion chr.1p, stage 1,2,5

s --- cure rate 90%

Second gr: older , more stage

Third gr: worse prognosis , 1-5 yr, advance stage,

n myc oncogene ,diploid, deletion chr. 1p ,mini Trk A

----- cure rate 5%

Micro homerise roset

Fluorescence in situ hybridization for N myc

Wlim’s tumor(nephroblastoma)- Most common childhood solid malignant tumor - Incidence 2-5 yr.- Survival rate > 90%- Asso three gr. malformation; aberration in chr 11p- 1) WARD syndrome : wilm’s ,aniridia,MR , genital

anomaly,deletion of 11p13 (WT-1 locus)- 2) Denys-Drash syndrome; gonodal dys.(male psuedohermaphroditism,nephropathy,wilm’s , missense

mutationof 11p13 (WT-1 locus) 3) Beckwith-Widerman syndrome: enlarge organ,

hemihypertrophy renal medullay cyst, wilm’s, adrcytomegaly , 11p15 (WT-2 locus)

Gross :large solid, well circum mass(10% bilat or multicentric) ,focal hem,cystic degeneration and necrosis

Micro: triphasic combination of

1.Blastemal com: primitive small blue cell. predominate------ stage 3 or 52.Stromal com: fibrocytic or myxoid stroma3. Epithelium com: abortive tubules and glomeruli, predomonate----- stage 1 5% of tumor analplasia (abn mitoses, pleo,hyper)----resistent Tx