Diseases of Infancy & Childhood
Major Time SpansNeonatal periodfirst four weeks of lifeInfancythe first year of lifeAge 1 – 4 yearsAge 5 – 14 years
MORTALITY by TIME SPAN
NEONATE (0-4 WEEKS): CONGENITAL, PREMATURITY UNDER ONE YEAR: CONGENITAL, PREMATURITY/WEIGHT, SIDS 1-4 YEARS: ACCIDENTS, CONGENITAL, TUMORS 5-14 YEARS: ACCIDENTS, TUMORS, HOMICIDES 15-24 YEARS: ACCIDENTS, HOMICIDE, SUICIDEMalformations primary errors of morphogenesis, usually multifactorial e.g. congenital heart defect Disruptions secondary disruptions of previously normal organ or body region e.g. amniotic bands Deformations extrinsic disturbance of development by biomechanical forces e.g. uterine constraint Sequence a pattern of cascade anomalies explained by a single localized initiating event with secondary defects in other organs e.g. Oligohydramnios (Or Potter) Sequence Syndrome a constellation of developmental abnormalities believed to be pathologically related e.g Turner syndrome
Malformations
Polydactyly & syndactylyCleft Lip
Severe Lethal Malformation
Disruption by an amniotic band
Oligohydramnios (Or Potter) Sequence
Oligohydramnios (decreased amniotic fluid) Renal agenesis Amniotic leak Fetal Compression flattened facies club foot (talipes equinovarus) Pulmonary hypoplasia fetal respiratory motions important for lung development Breech PresentationThe Oligohydramnios “Sequence”
Infant with oligohydramnios sequenceOrgan Specific Anomalies
Agenesis: complete absence of an organ Atresia: absence of an opening Hypoplasia: incomplete development or under- development of an organ with decreased numbers of cells Hyperplasia: overdevelopment of an organ associated with increased numbers of cells Hypertrophy: increase in size with no change in number of cells Dysplasia: in the context of malformations (versus neoplasia) describes an abnormal organization of cellsCAUSES OF ANOMALIES
Genetic karyotypic aberrations single gene mutations Environmental infection maternal disease drugs and chemicals irradiation Multifactorial UnknownEmbryonic Development
Embryonic period weeks 1- 8 of pregnancy organogenesis occurs in this period Fetal period weeks 9 to 38 marked by further growth and maturationCritical Periods Of Development
Genetic CausesKaryotypic abnormalities 80-90% of fetuses with aneuploidy die in utero trisomy 21 (Down syndrome) most common karyotypic abnormality (21,18,13) sex chromosome abnormalities next most common (Turner and Klinefelter) autosomal chromosomal deletion usually lethal karyotyping frequently done with aborted fetuses with repeated abortions Single gene mutations
Maternal Viral Infection
Rubella (German measles) at risk period first 16 weeks gestation defects in lens (cataracts), heart, and CNS (deafness and mental retardation) rubella immune status important part of prenatal workup Cytomegalovirus most common fetal infection highest at risk period is second trimester central nervous system infection predominatesDrugs and Chemicals
Drugs 13 cis-retinoic acid (acne agent) warfarin angiotensin converting enzyme inhibitors (ACEI) anticonvulsants oral diabetic agents thalidomide Alcohol TobaccoDiabetes Mellitus
Fetal Macrosomy (>10 pounds) maternal hyperglycemia increases insulin secretion by fetal pancreas, insulin acts with growth hormone effects Diabetic Embryopathy most crucial period is immediately post fertilization malformations increased 4-10 fold with uncontrolled diabetes, involving heart and CNS Oral agents not approved in pregnancy Diabetics attempting to conceive should be placed on insulinPerinatal Infection
Transcervical (ascending)inhalation of infected amniotic fluidpneumonia, sepsis, meningitiscommonly occurs with PROMpassage through infected birth canalherpes virus– caesarian section for active herpesTransplacental (hematogenous)mostly viral and parasiticHIV—at delivery with maternal to fetal transfusionTORCHparvovirus B19 (Fifth), erythema infectiosum bacterialListeria monocytogenesInborn Errors of Metabolism (Genetic)
PhenylKetonUria (PKU) Galactosemia Cystic Fibrosis (CF) (Mucoviscidosis)
PHENYLKETONURIA (PKU)
Ethnic distribution common in persons of Scandinavian descent uncommon in persons of African-American and Jewish descent Autosomal recessive Phenylalanine hydroxylase deficiency leads to hyperphenylalaninemia, brain damage, and mental retardation Phenylananine metabolites are excreted in the urine Treatment is phenylalanine restriction Variant forms existGALACTOSEMIA
Autosomal recessive Lactose → glucose + galactoseGalactose-1-phosphate uridyl transferase (GALT)GALT is involved in the first step in the transformation of galactose to glucoseabsence of GALT activity → galactosemiaSymptoms appear with milk ingestionliver (fatty change and fibrosis), lens of eye (cataracts), and brain damage involved (mechanism unknown)Diagnosis suggested by reducing sugar in urine and confirmed by GALT assay in tissueTreatment is removal of galactose from diet for at least the two first years of lifeCystic Fibrosis (Mucoviscidosis)
Autosomal recessive Most common lethal genetic disease affecting Caucasians (1 in 3,200 live births in the USA) 2-4% of population are carriers Uncommon in Asians and African-Americans Widespread disorder in epithelial chloride transport affecting fluid secretion in exocrine glands epithelial lining of the respiratory, gastrointestinal, and reproductive tracts Abnormally viscid mucus secretionsEtiology & pathogenesis: The primary defect is in the regulation of epithelial chloride transport by a chloride channel protein encoded by the cystic fibrosis gene. The impact of this defect in chloride transport differs in various tissue example: In sweat gland ducts it leads to decreased reabsorption of sodium chloride from the lumen, thus resulting in increase concentrations of sweat chloride, the basis of clinical diagnosis of CF
Cellular Metabolism Of The Cystic Fibrosis Transmembrane Regulator (CFTR)
Harrison’s Internal Med, 16th EdIn the airway epithelium: there is reduction of chloride secretion into airways. Active sodium absorption is also increase, both of these ions increase water reabsorption from the lumen causing lowering the water content of the mucus material leading to viscid secretions The cystic fibrosis gene is located on chromosome 7 which encodes chloride channel protein.
Pancreatic abnormalities are present in approximately 85 to 90% of patients. Thick viscid plugs of mucus may also be found in the small intestine of infants. Sometimes these cause small bowel obstruction, known as meconium ileus. The salivary glands are frequently involved, with histologic changes include progressive dilation of ducts, squamous metaplasia of the lining epithelium, and glandular atrophy followed by fibrosis.
In most cases, the diagnosis of cystic fibrosis is based on persistently elevated sweat electrolyte concentrations (often the mother makes the diagnosis because her infant tastes salty) and characteristic clinical findings (gastrointestinal or pulmonary) or a family history There are new reports suggesting an increased risk of digestive tract cancer in patients with cystic fibrosis. These cancers affect the entire gastrointestinal system, the biliary tract, liver, and pancreas. The pathenogenesis of such cancers is unclear.
The pulmonary changes are seen in almost every case and are the most serious complications of this disease. These stem from the viscous mucus secretions of the submucosal glands of the respiratory tree with secondary obstruction and infection of the air passages. obstruction of the epididymis and vas deferens, which is responsible for azoospermia and infertility in 95% of the males who survive to adulthood.