Disease Of Infancy And Childhood Flashcards by joseph dizon

Congenital anomalies

Multifactorial in origin

Malformations

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Congenital anomalies

Result from secondary destruction of an organ or body region that was previously normal in development.

Disruptions

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Congenital anomalies

Localized or generalized compression of the growing fetus by abnormal biochemical forces, leading to structural abnormalities.

Deformations

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Congenital anomalies

Cascade anomalies triggered by one initiating aberration

Sequence

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Congenital anomalies

Usually occur singly: sometimes multiple

Sequence

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Congenital anomalies

Extrinsic disturbance in morphogenesis

Disruptions

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Congenital anomalies

Example of malformations

Congenital heart defects

Anencephaly (absence of brain)

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Congenital anomalies

Example of disruptions

Amniotic bands

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Congenital anomalies

Example of deformations

Club feet

Uterine constraint

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Congenital anomalies

35-38th week gestations, rapid increase in the size of the fetus outspaces growth of uterus and decrease amniotic fluid.

Deformations

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Congenital anomalies

Example of sequence

Oligohydramnios

Potter sequence

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Cannot be explained on single initiating defect

Most often caused a single etiologic agent.

Malformation syndrome

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Malformation syndrome

Causes of anomalies

Genetic
Environmental
Multifactorial

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Malformation syndrome

80-90% of fetuses with aneuploidy and other abnormalities of chromosome number die in utero, the majority in the earliest stages of gestation.

Genetic causes

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Malformation syndrome

Genetics follow _____________ pattern of inheritance

Mendelian

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Malformation syndrome

Genetics

How many percent are autosomal dominant or recessive and xlinked

90% autosomal and recessive

10% x linked

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Malformation syndrome
Genetics

Most common developmental defect of the forebrain and midface.

Holoprosencephaly

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Malformation syndrome
Genetics

A critical role in morphogenesis and loss of function mutations

Hedgehog signaling

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Malformation syndrome

Environmental causes

At risk period shortly before conception to the 16th week of gestation, greater hazard in the first 8weeks.

Rubella

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Malformation syndrome

Environmental causes

Congenital rubella

Cataracts
Heart defects
Deafness
Mental retardation

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Malformation syndrome

Environmental causes

Mostly asymptomatic
Most common fetal viral infection

Intrauterine CMV infection

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Malformation syndrome

Environmental cause

CMV highest risk during

Second semester

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Malformation syndrome

Environmental causes

CMV is CNS involvement is a major feature are

Mental retardation
Microcephaly
Deafness
Hepatosplenomegaly

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Malformation syndrome

Less than 1% congenital malformations

Teratogens

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Malformation syndrome Drugs and other Chemicals Most widely used teratogen

Alcohol

Malformation syndrome Drugs and other Chemicals Alcohol disrupts 2 signaling pathways

Hedgehog | Retinoic acid

Malformation syndrome Drugs and other Chemicals Spontaneous abortion, premature labor placental abnormalities; low birth weight babies, and prone to sudden infant syndrome

Nicotine

Malformation syndrome Drugs and other Chemicals Radiation

Microcephaly Blindness Skill defects Spina bifida

Malformation syndrome Drugs and other Chemicals Maternal diabetes

Cardiac anomalies Neural tube defects CNS malformations

Malformation syndrome Drugs and other Chemicals Organomegaly and increase body fat and mass

Maternal diabetes

Malformation syndrome Drugs and other Chemicals Most common genetic causes of congenital malformation Cleft lip and palate Neural tube defect (folic acid)

Multifactorial inheritance

Two phases of intrauterine fetal developmant

Embryonic period - 1st 9weeks of pregnancy | Early embryonic period - 1st 3weeks after fertilization - abortion and death

Extremely susceptibility to teratogenesis, peaks at 4th-5th week

3rd-9thweek

Growth retardation, injury to already formed organs

Fetal period until birth

Craniofacial abnormalities including holoproncephaly and cyclopia (single fused eye)

Cyclophosphamide

HOX proteins | HOX mutations

Valproic acid

2nd most common cause of neonatal mortality | AOG

Prematurity

Major risk factors of prematurity

PPROM Intra uterine infection Uterine, cervical and placental abnormalities Multiple gestation

Responsible for as many as third of all preterm deliveries

PPROM

PPROM refers to spontaneous ROM occuring before

37 week

In contrast to PPROM. PROM rupture of membranes after

37weeks

Pathophysiology of PPROM

Inflammation of placental membranes, | Enhanced collagen degradation by MMP

PPROm risk factors

Smoking HS of vaginal bleeding Low socioeconomic status

Major cause of premature labor with or without intact membranes Present at 25% preterm births

Intrauterine infection

Example of intrauterine infection

Chorioamnionitis (inflammation of placental membranes) | Funisitis ( inflammation of fetal umbilical cord )

Most common microorganism of intra uterine infection

``` U. Urealyticum Mycoplasma hominis G. Vaginalis Trichomonas Gonorrhea Chlamydia ```

Hyaline membrane disease NecrotiIng enterocolitis Sepsis Intra ventricular and germinal matrix hemorrhage

Hazards of prematurity

Neonatal respiratory distress syndrome

Hyaline membrane disease

Infants who weights less than 2500gm are born at term (small for gestational age) suffers from

FGR fetal growth restriction

Factors known to result to FGR

Fetal abnormalities Placental abnormality Maternal abnormality Confined placental mosaicism

Fetal abnormalities

Chromosomal disorders Congenital anomalies Congenital/fetal infections

Congenital /fetal infections considered in all infants with FGR

TORCH ``` Toxoplasmosis Other viruses and bacteria Rubella CMV Herpes ```

Proportionate FGR, meaning all organ systems are similarly affected

SGA

Asymmetric, disproportionate GR with relative sparing of the brains

Placental abnormality

Placental abnormality usually during

3rd trimester

Placental abnormality

Placenta previa Thrombosis Multiple gestation

Most common factors associated with SGA

Maternal abnormality

Maternal abnormality conditions that result in decreased placental blood flow.

Pre eclapmsia Narcotic abuse Malnutrition Etc

Recently discovered causes of FGR | Mutations occur later and within the dividing trophoblast or extra embryonic progenitor cells

Confined placental mosaicism

Most common cause is respiratory distress syndrome also known as hyaline membrane disease

Neonatal respiratory distress syndrome

Major cause of NRDS

Sedation of mother Fetal head injury Aspiration of Blood Hypoxia

Clinical findings of NRDS

Preterm Male DM CS

Dx of NDRS

Fine rhales | Ground glass picture

Pathogenesis of NRDS

Immaturity of the lungs | RDS inversely proportional with gestational age

Etiology of NDRS

Deficiency of lung surfactant-fundamental defects in RD Di palmitoyl phosphatidyl choline Phosphatidyl glycerol Surfactant associated proteins

Severe respiratory failure in neonates with congenital deficiency of surfactant caused by

Mutation of SFTPB and SFTBC

Surfactant is accelerated after

35th week of gestation

Compounded by soft thoracic wall that I spelled in as diaphragm descend q

Stiff atelectatic lung

Barriers to gas exchange leading to carbon dioxide retention and Hypoxemia

Fibrin hyaline membranes

Surfactant synthesis is modulated by

``` Cortisol Insulin Prolactin Thyroxine TGF-B ```

Intrauterine stress and FGR increase

Corticosteroid and lower risk for RDS

Labor increase what

Surfactant of synthesis

Before onset of labor may increase risk of RDS

CS section.

Gross of RDS

Normal size Solid Airless Reddish purple liver

RDS microscopic

Poorly developed alveoli with atelectasis

Major thrust in control of RDS is focuses or prevention either

Delaying labor until fetal lung reaches maturity

Prophylactic administration of exogenous surfactant at birth to extremely premature infants has been shown very beneficial

Less than 28 weeks of gestation

RDS 2 known complication

Retrolental fibroplasia | Bronchoplumonary Dysplasia

RDS Anternal corticosteroids to mothers with threatened preterm delivery at

24-34 weeks

Retrolental fibroplasia has 2 phase pathogensis

Phase 1- hyperoxic phase RDS | Phase 2 - hypoxic room air ventilation

VEGF decreased

Phase 1

VEGF increased

Phase 2

RDS Caused by impairment in the development of alveolar septation

BPD | Bronchoplumonary Dysplasia

Infant who recover from RDS, have increase risk of

PDA Intraventricular hemorrhage Necrotizing enterocolitis

Most common premature infants; inversely proportional to gestational age

Necrotizing enterocolitis

NEC Multifactorial in etiology

Premature Enteral feeding Infections

NEC manifestations

Bloody stools Abdominal distention Circulatory collapse Gas within the intestinal wall

NEC gross

Distented part Gangrenous Intestinal perforation Peritonitis

NEC microscopic

Transmural coagulation necrosis Ulceration Bacterial colonization and Submucosal gas bubbles

NEC treatment

Conservatively 20-60% resection of the bowel

Usually acquired by cervicovaginal route | Most bacteria and virus (herpes simplexII )

Transcervical (ascending) infection

Transcervical In general fetus acquires infection either by

Inhaling of infected amniotic fluid shortly before birth By passing thru the infected birth canal

Transcervical Preterm birth is common and unfortunate consequence of infection due to

Damage and rupture of amniotic sac as consequence of inflammation Prostaglandins released from neutrophils

Transcervical | Inhalation of amniotic fluid

Pneumonia | Sepsis and meningitis

Hematogenous gain access thru chorionic villi

Transplacental (hematologic) infections

Transplacental Chorionic villi

Parasitic (toxoplasma, malaria) | Bacterial (listeria, treponema)

Transplacental May occur at any time during gestation

Hep B and HIV

Transplacental Delivery via maternal-fetal transfusion

Parvovirus B 19 | TORCH

Erythema infectious 5th disease of childhood | Can infect seronegative (non immune) pregnant women

Parvovirus B19

Early onset within 1st 7days of life

Perinatal sepsis

Most common cause of early onset sepsis

Group B strep

Perinatal sepsis from 7days to 3 months

Late onset Listeria Candida

Accumulation of edema fluid in fetus during intrauterine growth Progressive and generalized edema of the fetus

Fetal hydrops

Most serious threat in fetal hydrops is CNS damage

Kernicterus

Kernicterus affected brain is enlarged and edematous

``` Basal ganglia Thalamus Cerebellum Cerebral gray matter Spinal cord ```

Fetal hydrops Clinical features Infants

Pallor | Hepatosplenomegaly

Fetal hydrops Clinical features Neonates

Jaundice Generalized edema Neurologic injury

Fetal hydrops These infants may be supported by

Phototherapy | Total exchange transfusion

Hemolytic diseases in the newborn caused by blood group incompatibility between mother and child.

Immune hydrops

Immune hydrops During

3rd trimester

Immune hydrops Initial exposure to _________ evokes the formation of ____

Rh antigen | IgM

Immune hydrops Exposure during a subsequent pregnancy generally leads to a brisk ___

IgG

Immune hydrops Concurrent ABO incompatibility protects the mother against Rh immunization because fetal RBC

Coated with ant A/B IgM

Immune hydrops Dose of immunizing antigen; hemolytic disease develops only when the mother has experienced a significant

Transplacental bleed

Immune hydrops Treatment and prevention

Administration of the Rhesus immune globulin (RhIg) containing anti D antibodies at 28 weeks and within 72 hours of delivery to the Rh negative mothers

Immune hydrops Antenatal identification and management of the at risk fetus have been greatly facilitated by

Amniocentesis | Fetal blood sampling

Immune hydrops ABO incompatibility

Mother O | Infant AB

Immune hydrops ABO incompatibility Do not cross placenta

Most anti A and B antibodies are of IGM type

Immune hydrops ABO incompatibility Certain group O women possess IgG antibodies directed against group A or B antigens even without

Prior sensitization

2 consequences of excessive RBC destruction in neonates

Anemia | Jaundice

Immune hydrops May result in hypoxic injury to the heart and liver Result in edema and anasarca, culminating in hydrops fetails

Anemia

Immune hydrops Jaundice

Unconjugated bilirubin Poorly developed BBB Damage CNS causing Kernicterus

Non immune hydrops

Cardiovascular Chromosome anomalies Fetal anemia

Non immune hydrops Most common cause of no immune hydrops

Fetal anemia due to homozygous alpha thalasemmia

Inborn errors of metabolism Most common form, common in persons of Scandinavian descent

PKU

PKU Enzyme def

Phenylalanine hydroxylase

PKU 6 months of life

Severe mental retardation

PKU Inability to convert

Phenylalanine to tyrosine

PKU Excreted in urine cause

Mousy odor

PKU Without tyrosine no

Melanin

Galactosemia Accumulation of

Galactose 1 phosphate in tissue

Galactosemia Two variants

Total lack of galactose 1 phosphate uridyl transferase (GALT) involved reaction 2 Deficiency of galactose, reaction 1

Galactosemia More common

Involved reaction 2

Galactosemia Milder form, not associated with mental retardation

Reaction 1

Galactosemia Product of excess galactose, that can accumulate to tissue

Galactitol | Galactonate

Galactosemia Clinical feature

``` Liver Eyes Brain Infants fail to thrive Vomiting and diarrhea ```

Galactosemia Clinical features 2

Amino aciduria E. coli Hemolysis and coagulopathy

Galactosemia Can prevent by

Early removal of galactose from diet for atleast the first 2 years of life

Galactosemia Older patient

Speech disorder Gonadal failure Ataxia

Autosomal recessive, Caucasian population

Cystic fibrosis/ mucoviscidosis

Cystic fibrosis/ mucoviscidosis Affect fluid secretion in

Exocrine glands | Epithelial lining of respi, GIT and reproductive tracts

Cystic fibrosis/ mucoviscidosis Abnormally viscous secretions which obstruct organ passages resulting in

``` Lung Pancreas Liver Intestine Steatorrhea Malnutrition Male infertility ```

Cystic fibrosis/ mucoviscidosis Primary defect

CL-channel protein CFTR gene on chromosome 7q31.2

Cystic fibrosis/ mucoviscidosis Most patho physiologic relevance in

Interaction with ENAC

Cystic fibrosis/ mucoviscidos CTFR functions

Regulate multiple ion channels and cellular processes Tissue specific Regulates transport of bicarbonate ions

Cystic fibrosis/ mucoviscidosis CFTR is one of the most important avenues for active

Luminal secretion of chloride

Cystic fibrosis/ mucoviscidosis Class of CFTR protein

Class 1- defective protein synthesis Class 2 - abnormal protein folding, processing, and trafficking Class 3- defective regulation Class 4- decreased conductance Class 5- reduced abundance Class 6- altered function in regulation of ion channels

Cystic fibrosis/ mucoviscidosis Produce virtual absence of membrane CFTR function are associated with the classic cystic fibrosis phenotype

Class 1,2&3

Cystic fibrosis/ mucoviscidosis Less severe

Class 4&5

Cystic fibrosis/ mucoviscidosis Remains one of the best known examples of the

One gene one disease

Cystic fibrosis/ mucoviscidosis Example of one gene one disease

Mannose binding lectin 2 | Transforming growth factor beta1

Cystic fibrosis/ mucoviscidosis Morphology

Pancreas Meconium ileus Liver Pulmonary changes (most serious)

Cystic fibrosis/ mucoviscidosis Clinical features

Meconium ileus Pancreatic insufficiency Cardiorespiratory complications Recurrent sino nasal polyps

Cystic fibrosis/ mucoviscidosis Diagnosis

Le aged sweat electrolyte concentration Abnormal newborn screening test Family history Clinical findings

A disease of unknown cause

Sudden infant death syndrome (SIDS)

Sudden infant death syndrome (SIDS) Unexplained after a thorough case of investigation

After an autopsy Examination of death scene Review of clinical history

Sudden infant death syndrome (SIDS) What position

Prone or side position Crib death or cot death

Sudden infant death syndrome (SIDS) Apparent life threatening event

Apnea Color or muscle tone Gagging

Sudden infant death syndrome (SIDS) Morphology

Multiple petechiaethymus

Sudden infant death syndrome (SIDS) Lungs

Congested and vascular engorgemnt with or without edema

Sudden infant death syndrome (SIDS) CNS

Astrogliosis of brain stem and cerebellum

Sudden infant death syndrome (SIDS) Triple risk of model of SIDS

Vulnerable infant Critical development period in homeostatic control Exogenous stressor

2% of all malignant tumors

Tumors and tumor like lesions of the infancy and childhood

Tumors and tumor like lesions of the infancy and childhood Normal cells present in abnormal locations

Heterotopia or choristoma

Tumors and tumor like lesions of the infancy and childhood Overgrowth of cells

Hamartomq

Tumors and tumor like lesions of the infancy and childhood Linkage between malformations and neoplasm

Hamartoma

Benign tumors and tumor like lesions Most common tumor of infancy

Hemangiomas

Benign tumors and tumor like lesions Hemangiomas in skin

Port wine stain

Benign tumors and tumor like lesions CNS hemangioma

Von hippel Lindau disease

Benign tumors and tumor like lesions Hamartomatous or neoplastic Occur in the skin but most often encountered in deeper regions of the neck, axilla

Lymphangiomas

Benign tumors and tumor like lesions Increases size after birth

Lymphangiomas

Benign tumors and tumor like lesions Do not extend beyond original location

Lymphangiectasis

Benign tumors and tumor like lesions Congenital infantile fibrosarcomas ETV6- NTRK3

Fibrous tumors

Benign tumors and tumor like lesions Benign well differentiated cystic lesions

Mature teratomas

Benign tumors and tumor like lesions Lesion of intermediate potential

Immature teratomas

Benign tumors and tumor like lesions Usually admixed with another germ cell tumor such as Endodermal sinus tumor

Malignant teratomas

Benign tumors and tumor like lesions Teratomas 2 peaks of incidence

2 years of age (congenital neoplasm) | Late adolescent or early adulthood

Benign tumors and tumor like lesions Most common teratomas in childhood

Sacrococcygeal teratomas Menigocele and spina bifida

Malignant tumors Most frequent childhood cancers arise in the

``` Hematopoietic system Nervous tissue Soft tissue Bone Kidney ```

Malignant tumors In adults, most common sites of tumors

``` Skin Lungs Breast Prostate Colon ```

Malignant tumors Most common extracranial solid tumor of childhood Most frequently diagnosed tumor of infancy

Neuroblastoma

Malignant tumors Median age of diagnosis

18 months

Malignant tumors Major cause familial predisposition to neuroblastoma

ALK germline mutation

Malignant tumors Larger cells having more abundant cytoplasm, large vesicular nuclei and prominent nucleoli ganglion cells

Ganglioneuroblastoma

Malignant tumors Maturation of neuroblast into ganglion cells Accompanied by Schwann cells

Ganglioneuroma

Malignant tumors Histologic prerequisite, with favorable outcome

Schwannian stroma

Malignant tumors In younger children

Abdominal mass Fever Weightloss

Malignant tumors In older children

Blueberry muffin baby

Malignant tumors Most pertinent prognostic factors include

Age and stage (mist important determinants of outcome) Morphology MYCN Ploidy less than 2 yo

Malignant tumors Most important genetic abnormality used in risk

MYCN

Most common primary renal tumor of childhood, 4th common pediatric malignancy

Wilms tumor

Wilms tumor Deletion of 11p13

WAGR syndrome Aniridia Genital anomalies Mental retardation

Wilms tumor Missense, zinc finger, gonadoblastomas

Denys-drash syndrome

Wilms tumor ``` Paternal allele (IGF-2) Maternal allele (loss of imprinting) ```

Beckwith- wiedemann syndrome Organomegaly

Congenital anomalies that has a primary errors of morphogenesis

Malformation