Diseases of Infancy and Childhood Flashcards
Malformation definition:
Malformations represent primary errors of morphogenesis.
Disruptions definition:
Ex:
Are they inheritable?
Result from secondary destruction of an organ or body region that was previously normal in development.
Amnion wraps around fetus’s extremities.
They are not inheritable.
Deformation definition:
Localized or generalized compression of growing fetus by abnormal biomechanical forces.
“Uterine constraint”.
What is the Potter sequence?
A sequence that leads to a cascade of anomalies triggered by one irritating aberration.
What is the pathway of the pathogenesis of oligohydramnios and the Potter sequence?
Renal agenesis, amniotic leak, others can cause hydramnios.
The hydramnios leads to fetal compression which can cause pulmonary hypoplasia, altered facies, strange positioning of the hands and feet and a breeched presentation.
What can lead to pulmonary hypoplasia? (2)
Oligohydramnios and fetal compression
What are amnion nodosum?
Caused by oligohydramnios and appear as which spots on the amnion.
Agensis
Failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue.
Aplasia
A birth defect, where an organ, or a tissue, is absent, or defective.
Atresia
Absence or abnormal narrowing of an opening or passage in the body.
Symptoms/presentations of children with FAS
Pre and post natal growth retardation Facial anomalies Psychomotor disturbances Microcephaly Low weight Hyperactivity Learning disabilities
What is the timeline of the embryonic period?
Weeks 3-8
Extremely preterm:
Very preterm:
Moderate to late preterm:
Extremely preterm: <28 wks
Very preterm: 28-32 wks
Moderate to late preterm: 32-37 wks
Risks for prematurity (4)
Preterm premature rupture of the membranes (PPROM)
Intrauterine infection
Uterus/cervix/placental abnormalities
Multiple gestation
Hyaline membrane disease is AKA:
Respiratory distress syndrome (RDS)
What are 3 associations with RDS?
Males
Maternal diabetes
C-section
Often resuscitation is needed for babies with RDS.
Post resuscitation, what do the babies do?
Breathing is labored and they can become cyanotic .
Rales are evident in BL lung fields.
CXR will show a ground-glass picture.
Main cause of RDS is deficiency of:
Pulmonary surfactant
What genes cause deficiency of surfactant?
SFTPB and SFTBC
At which phase of lung development, and which week, does surfactant begin to form?
What part of the lung must be produced before surfactant is produced?
Saccular phase
Wk 25 approx.
Alveolar ducts.
What is necrotizing enterocolitis?
An condition that occurs in very low birth weight babies most often. It is likely caused by infection, but it hasn’t been pin-pointed to one pathogen.
Which mediator is known to increase mucosal permeability and is associated with necrotizing enterocolitis?
PAF
What is the clinical course of NEC?
What do XRs show?
Bloody stools, abdominal distension and circulatory collapse.
Gas within the intestinal wall (pneumatosis intestinalis).
Retrolental fibroplasia is associated with:
VEGF
Bronchopulmonary dysplasia leads to activation of which proinflammatory cytokines? (4)
What do these cytokines cause?
TNF, IL-1b, IL-6, IL-8.
Arrest of alveolar development.
What is the treatment for BPD?
Surfactant and steroids
NEC involves which parts of the colon?
How does it look?
What kind of necrosis can occur?
Terminal ileum, cecum and right colon.
Distended, friable and congested.
Gangrenous, and coagulative microscopically.
What is the most common diagnostic sign in patients with NEC?
Pneumatosis intestinalis
What virus is associated with perinatal infection?
Parvovirus B19
What symptoms are involved in TORCH infections?
Fever Encephalitis Chorioretinitis Hepatosplenomegaly Pneumonitis Myocarditis Hemolytic anemia Hemorrhagic skin lesions
What is fetal hydrops?
Accumulation of edema in 2 or more fetal compartments during intrauterine growth (pleural, peritoneal, ascites, skin, etc).
Non-immune.
What is cystic hygroma?
Localized accumulation of fluid in a fetus.
Seen in Turner’s syndrome.
Non-immune.
Immune hydrops
Disease caused by blood group Ag incompatibility between mom and fetus
How does immune hydrops occur?
When baby’s RBC antigenic determinants (Rh) are from the father and foreign to the mother, the mom has an immune reaction.
When does the immune hydrops reaction occur?
In what gentoypic mother and father?
The second and subsequent pregnancies.
Mom is Rh- and Dad is Rh+ -> baby is Rh+.
What can happen to the baby as a result of removal and destruction of the RBC-Ab complex in immune hydrops in the baby? (4)
Anemia
Hydrops
*Extramedullary hematopoiesis - seen in histology
Bilirubin -> jaundice and kernicterus
Non-immune hydrops have which 3 major eitiologies?
- CV defects: structural and functional anomalies.
- Chromosomal anomalies: 45X, trisomy 21 and 18.
- Fetal anemia (not Rh or ABO): alpha thalassemia, transplacental parvo B19 and twin-twin transfusion.
What kind of abnormalities suggest inborn errors of metabolism?
Dysmorphic featurs Deafness Self-mutilation Hydrops Abnormal body or urine odor Hypo/hypertonia Seizures Poor feeding Vomiting Jaundice Cataracts Red macula Myopathy Joint stiffness
How does CF lead to a salty baby?
The Cl- cannot enter the epithelial cells of sweat ducts, so it can go back out to the skin.
In all variants of CF, what is unaffected?
Sweat glands
What is virtually always present in a patient with CF?
Pancreatic insufficiency
Atrophy of what part of the pancreas occurs in the pancreas?
What does it impair?
What associated deficiency may contribute to squamous metaplasia?
Exocrine portion
Impairs fat absorption.
Vit A
What 3 bugs are the most common cause of lung infections?
What is the most common bug in CF?
Staph aureas
Haemophilis influenzae
Pseudomonas aeruginosa
B. cenocepacia
SIDS is a diagnosis of:
Exclusion and always warrants an autopsy
Pathogenesis of SIDS requires what 3 things?
- Vulnerable infant
- Critical developmental period in homeostatic control
- An exogenous stressor
What can develop on organs post mortem?
On which organs?
Petechiae
Lungs, thymus, heart
Heterotopia (choristoma)
Normal cells in an abnormal location
Hamartoma
Excessive focal overgrowth of tissue native to that organ
What is the most common tumor of infancy?
Do they go away?
Capillary hemangiomas, portal wine stain
Yes oftentimes they do
Benign lymphatic tumors in kids (2)
Lymphangioma
Lymphangiectasia
Benign fibrous tumors in kids (1)
Can look like fibrosarcoma in adults, but do better
What is the most common teratoma in kids?
M/F more likely to get it?
Sacrococcygeal teratoma
F>M, 4:1
Malignancies of non-hematopoietic pediatric neoplasms are unique because (include the morphology):
What are they called?
They have an embryonic, undifferentiated appearance, characterized by sheets of cells with small, round nuclei and show features of organogenesis.
Blastomas
What is the most common extracranial tumor of childhood?
What is the median age of diagnosis?
Neuroblastoma
18 mo
Clinical presentation of a child with Neuroblastoma
<2 y/o w/ large abdominal mass, fever and weight loss.
Cutaneous mets -> blueberry muffin baby.
> 2 y/o may present w/ mets (blood and lymphatic)
Periorbital region is a common site of metastasis.
What is the most important diagnostic feature of neuroblastomas?
How do you test this? (3)
High production of catecholamines.
Check catecholamines in blood and VMA and HVA in urine.
What are Homer-Wright pseudorosettes?
Appear in neuroblastoma where differentiated cells surround neuropil.
Favorable and non-favorable levels of mitosis-karyorrhexis index for prognosis of neuroblastoma:
Favorable: <200/5000 cells
Nonfavorable: >200/5000 cells
Is it favorable or nonfavorable to have evidence of schwannian stroma and gangliocytic differentiation present?
Yes, favorable
What is chromothripsis?
Extensive genomic rearrangements and an oscillating pattern of DNA copy levels, usually restricted to one or a few chromosomes.
Found in aggressive neuroblastomas.
Wilms tumor presentation:
What is often present at the time of DX?
Large abdominal mass
Hematuria
Intestinal obstruction
HTN appearance
Pulmonary mets.
Morphology of Wilms tumor
Large well-circumscribed mass (10% BL)
Cut surface is soft, homogenous and tan-gray
Can have necrosis, cyst formation or hemorrhage.
The vast majority of WIlms tumors contain a classic triphasic combo (on histology) of:
Blastemal cells
Stromal cells
Epithelial cell types
3 recognizable groups associated with distinct chromosomal loci associated w/ a Wilms tumor:
- WAG/WAGI syndrome
- Denys-Drash syndrome
- Beckwith-Wiedeman syndrome
WAG/WAGI syndrome Risk level: Deletion of which gene? WAGR acronym: WT1 PAX6
What is the first hit? Second hit?
33% risk.
Deletion of 11p13.
Wilms tumor, aniridia, genital abnormalities, MR.
WT1: Wilms tumor associated gene
PAX6: provides instructions for making a protein that is involved in early development of the eyes, spinal cord and pancreas.
First hit is deletion of WT1 and second hit is a frameshift or nonsense mutation in second allele.
Denys-Drash syndrome
Risk level:
Presentations (2):
Increased risk of?
90% risk. Gonadal dysgenesis (male pseudohermaphrodism) and renal failure. Increased risk for gonadoblastoma.
Beckwith-Wiedeman syndrome sx (5)
What is it an example of?
What is often mutated in this syndrome?
Increased risk of? (4)
Organomegaly, macroglossia, hemihypertrophy, omphocele, adrenal cytomegaly.
Genomic imprinting.
CDKN1C mutation - a cell cycle regulator (p57) that broadly inhibits CDKs.
Increased risk for hepatoblastoma, pancreatoblastoma, adrenal cortical tumors, rhabdomyosarcoma.
3 major categories of congenital anomalies
Genetic
Environmental
Multifactorial
What abnormalities can cause SGA and lead to FGR?
Fetal abnormalities
Placental abnormalities
Maternal abnormalities
What are the two big complications of RDS and their pathophysiology?
Retrolental fibroplasia: retinopathy of prematurity due to decreased VEGF in the eyes.
Bronchopulmonary dysplasia: due to increased IL-1B, -6, -8.
Infants who recover from RDS are at an increased risk for? (3)
PDA
Intraventricular hemorrhage
Necrotizing enterocolitis
What is the affect of PAF on NEC?
It increases mucosal permeability by promoting enterocyte apoptosis and compromising tight junctions —> inflammation, mucosal necrosis, bacterial infiltration —> sepsis and shock.
Minimally affected children with nonimmune hydrops will display:
Severely affected children?
Minimally affected will display pallor and hepatosplenomegaly.
Severely affected will present with jaundice, edema and signs of neurological damage.
What are the two primary routes for perinatal infection?
Transcervically and transplacentally
Galactosemia is a deficiency in:
Presentation:
GALT leadingto accumulation of galactose-1-phosphate.
Hepatomegaly, opacification of lens, nonspecific CNS problems, failure to thrive, vomiting, diarrhea, jaundice.
Morphological features of SIDS
Petechiae
Extramedullary hematopoiesis
CNS astrogliosis of brain and cerebellum
Benign tumors of childhood (4)
Hemangiomas
Lymphatic tumors - lymphangiomas, lymphangiectasis
Fibrous tumors
Teratomas
Where majority of neuroblastomas arise?
Adrenal medulla
Synchronous vs. metachronous
Synchronous means both organs affected at same time. Metachronous means both organs affected in succession.
Incidence of Wilms tumors
1/10k
4th most common pediatric tumor in USA.
What are nephrogenic rests?
Lesions that are precursors to Wilms tumors.
Seen in approx 25-40% of UL tumors and almost 100% of BL tumors.
