Chapter 10 Flashcards
Primary cause of death in infants younger than 1 year
Congenital malformations, deformations, and chromosomal abnormalities
Primary cause of death in children age 1-4
Accidents (unintentional injury)
Primary cause of death in children 5-9
Accidents (unintentional injury)
Primary cause of death in children 10-14
Accidents (unintentional injury)
Primary errors of morphogenesis in which there is intrinsically abnormal developmental process; typically multifactorial in origin
Malformations
Examples of malformations
Congenital heart defects
Anencephaly
Polydactyly or syndactyly
Cleft palate
_____ result from secondary destruction of an organ or body region previously normal in development; arise from extrinsic disturbance in morphogenesis
Disruption
Examples of disruption
Amniotic bands
Example of deformation
Clubfeet
Fetal phenotype associated with Potter sequence
Flattened facies Positional abnormalities of hands and feet Hips may be dislocated Hypoplastic lungs Nodules in amnion
General cause of holoprosencephaly
Genetic — mendelian inheritance
Clinical features of fetal alcohol syndrome
Growth retardation Microcephaly Short palpebral fissures Maxillary hypoplasia Psychomotor disturbance
Etiology/associations with neonatal respiratory distress syndrome
Excess sedation of mother, fetal head injury during delivery, aspiration of blood or amniotic fluid, intrauterine hypoxia from cord around neck
Associated with male gender, maternal diabetes, and delivery by C section
What therapy can be administered prior to birth if the fetuses lungs are underdeveloped?
Glucocorticoids
2 major complications of ventilation used to treat neonatal RDS
Retinopathy of prematurity (retrolental fibroplasia) — leads to retinal vessel proliferation
Bronchopulmonary dysplasia — striking decrease in alveolar septation
Infants who recover from neonatal RDS are at increased risk for what conditions?
Patent ductus arteriosus
Intraventricular hemorrhage
Necrotizing enterocolitis
Etiology/associations with necrotizing enterocolitis
Most common in premature infants
Most cases associated with enteral feeding, suggesting that some postnatal insult (like introduction of bacteria) causes tissue destruction process
Inflammatory mediators
What inflammatory mediator is implicated in necrotizing enterocolitis — playing a role in increasing mucosal permeability by promoting enterocyte apoptosis and compromising intercellular tight junctions?
PAF
Define fetal hydrops and differentiate immune vs. nonimmune
Fetal hydrops = accumulation of edema fluid in fetus during intrauterine growth
Immune: type II HSR associated with Rh-group incompatibility
Nonimmune: most commonly associated with cardiovascular issues, chromosomal issues, or fetal anemia
Morphology and clinical features of fetal hydrops
Pale fetus and placenta
Hepatosplenomegaly
Hyperplastic erythroid precursors in bone marrow
Extramedullary hematopoiesis in liver, spleen, kidneys, etc.
Jaundice d/t unconjugated bili
Kernicterus
2 primary routes by which perinatal infections are acquired
Transcervically — most bacterial and a few viral; inhalation of infected amniotic fluid or passing through infected birth canal
Transplacentally (hematologic) — most parasitic and viral, some bacterial (listeria, treponema); gain access to fetal bloodstream via chorionic villi
Transplacentally acquired pathogen resulting in erythema infectiosum, characterized by spontaneous abortion, stillbirth, hydrops fetalis, and congenital anemia
Parvovirus B19
Describe TORCH group of infections in terms of clinical features and chronic sequelae
Fever, encephalitis, chorioretinitis, HSM, pneumonitis, myocarditis, hemolytic anemia, vesicular or hemorrhagic skin lesions
Chronic sequelae: growth and mental retardation, cataracts, congenital cardiac anomalies, bone defects
Enzyme deficiency and clinical presentation of PKU
Enzyme def: PAH
Clinical presentation: hyperphenylalaninemia — severe mental retardation by 6 mos, seizures and other neurologic problems, decreased pigmentation of hair and skin, eczema, strong musty odor to urine
Enzyme deficiency and clinical presentation of galactosemia
2 possible enzyme def: most common is lack of galactose-1-phosphate uridyl transferase (GALT), rare is deficiency of galactokinase
Results in accumulation of galactose-1-phosphate in liver, spleen, lens, kidneys, heart muscle, cerebral cortex, and erythrocytes. Also accumulation of galactitol and galactonate in tissues.
Liver, eyes, and brain get worst damage — hepatomegaly, cataracts, loss of nerve cells, gliosis, brainstem edema
Others: FTT, vomiting, diarrhea within a few days of milk ingestion, persistent jaundice, mental retardation within 6-12 mos, aminoaciduria, E coli septicemia, hemolysis, and coagulopathy
Inheritance of PKU and galactosemia
AR
Inheritance of CF
AR
CF is associated with what other conditions that may harbor CFTR mutations?
Idiopathic chronic pancreatitis
Late-onset chronic pulmonary disease
Idiopathic bronchiectasis
Obstructive azoospermia
Changes in airway vs. sweat cell transport in CF
Airway: ENaC activity increases, markedly augmenting Na uptake across apical membrane
Sweat glands: ENaC activity decreases, producing salty sweat
Result of possibly abnormal bicarbonate conductance in CF
Decreased luminal pH —> pancreatic insufficiency
Congenital absence of vas deferens is associated with what condition?
CF
Clinical features of CF
Chronic lung disease secondary to recurrent infections (common agent is pseudomonas aeruginosa —> lower lungs) and recurrent sinonasal polyps
Pancreatic insufficiency (results in ADEK deficiency and edema)
Steatorrhea and hepatic cirrhosis
Malnutrition characterized by large, foul smelling stools, abdominal distension, and poor weight gain
Intestinal obstruction (meconium ileus), polyposis
Male infertility
Morphological findings in SIDS cases
Multiple petechiae
Congested lungs with vascular engorgement +/- pulmonary edema
Astrogliosis of brainstem and cerebellum
Persistent hepatic extramedullary hematopoiesis and periadrenal brown fat
Delineate heterotopia from hamartoma
Heterotopia (choristoma): microscopically normal cells or tissues that are present in abnormal locations
Hamartoma: excessive focal overgrowth of cells and tissues native to the area in which it occurs
2 types of lymphatic tumors of childhood
Lymphangiomas: hamartomatous or neoplasic; characterized by cystic and cavernous spaces, tend to increase in size after birth
Lymphangiectasis: represent abnormal dilations of preexisting lymph channels, usually presents as diffuse swelling of part or all of an extremity
2 types of fibrous tumors seen in childhood
Fibromatosis: sparsely cellular proliferations of spindle-shaped cells
Congenital-infantile fibrosarcomas: richly cellular lesions indistinguishable from fibrosarcomas in adults
Characteristic chromosomal translocation associated with congenital-infantile fibrosarcomas
t(12;15)(p13;q25) - results in generation of ETV6-NTRK3 fusion transcript
Sites of involvement for neuroblastic tumors
Sympathetic ganglia
Adrenal medulla
Morphologic features of neuroblastic tumors
Presence of neuropil on histology, as well as Homer Wright pseudorosettes
Presence of ganglion cells + primitive neuroblasts = ganglioneuroblastoma
Presence of ganglion cells without neuroblasts = ganglioneuroma
Clinical course of neuroblastic tumors
Large abdominal masses, fever, possibly weight loss
Metastasize widely — liver, lungs, bones, bone marrow, periorbital region, skin “blueberry muffin baby”
Production of catecholamines = important diagnostic feature is VMA and HVA
Favorable prognostic factors for neuroblastic tumors
Stage 1, 2A, 2B, 4S Age <18 mos Presence of schwannian stroma and gangliocytic differentiation Low mitosis-karyorrhexis index Hyperdiploid (whole chromosome gains) No amplification of MYCN No loss of Chr 1p or 11q Presence of TRKA expression No TRKB expression or mutations of neuritogenesis genes
3 groups/types of Wilms tumor and their identifying feature(s)
- WAGR syndrome - WT1 deletion, aniridia, genital anomalies, mental retardation
- Denys-Drash syndrome - gonadal dysgenesis, renal failure, risk of gonadoblastoma, precursors are nephrogenic rests; missense mutation in WT1
- Beckwith-Wiedmann syndrome - organomegaly, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly; heterogenous abnormalities in 11p15.5
In which group of Wilms tumor is there increased risk of rhabdomyosarcoma, hepatoblastoma, pancreatoblastoma, and adrenocortical tumors?
Beckwith-wiedmann syndrome
Wilms tumor, what is the difference if it is caused by germline mutations vs. sporadic mutations?
Germline —> bilateral masses
Sporadic —> unilateral
Morphologic features of wilms tumor
Classic triphasic combo of blastemal, stromal, and epithelial cell types
Some tumors show anaplasia, usually with TP53 mutations (confers resistance to chemo)
Clinical course of wilms tumor
Most present with large abdominal mass that may be unilateral or grow to extend over midline
Hematuria, abdominal pain, intestinal obstruction, HTN
Pulmonary metastases common at time of dx
