Diseases of Infancy and Childhood Flashcards
How do we fix a child that has atelectasis or RDS?
glucocorticoids
Clinical course an prognostic features of neuroblastoma:
1) what is the most important determinants of outcome? What’s the exception to one of them?
2) what’s the critical period for age?
3) what morphology leads to a great prognosis?
4) what about MYCN amplification?
5) ploidy? which is more aggressive? what’s
6) What aout mitosis-karyorrhexis index?
Age and Stage: 1, 2A or 2B = great at any age… EXCEPT HIGH AMPLIFICATION OF MYCN
18 months or younger = great prognosis
schwannian Stroma and gangliocytic differentiation
if there is amplification, BAD Prognosis REGARDLESS OF AGE
near diploid is more aggressive than hyperploidy –> segmental chromosomal loss (rather than whole chromosome) –> “chromothripsis –> localized loss that can amplify MYCN
more than 200/5000 cells
Prematurity:
definition
what are he 4 major risk factors associated with it?
a gestational age less than 37 weeks
1) PPROM: Preterm Premature Rupture of Placental Membranes –> spontaneous ROM occurring before 37 weeks
2) Intrauterine infection –> chorioamnionitis (inflammation of placenta), funisitis (inflammation of the fetal umbilical cord). –> most common are Ureaplasma urealyticum,
3) uterus/cervix/placental abnormalities
4) multiple gestations
PKU:
1) who is affected
2) what’s the problem
3) what genotype
4) what do kids present with and at what time
5) 2% of the population has what abnormality that can also give PKU?
scandinavian descent
deficiency in phenylalanine hydroxylase (PAH) –> buildup of phenylalanine.
autosomal recessive
6 months, severe mental retardation. Seizures, decreased pigmentation of hair and skin, and eczema
BH4 (tetrahydrobiopterin) recycling or synthesis.
Neuroblastic tumors:
what are they the most common of?
most common sites of involvement
what do all neuroblastic have in common?
Prevalence
EXTRACRANIAL solid tumor of childhood
tumors of the sympathetic ganglia and adrenal medulla (hence present with abdominal problems) that are derived from primordial neural crest cells populating these sites.
spontaneous or therapy induced differentiation of primitive neuroblasts into mature elements, spontaneous tumor regression, and a wide range of clinical behavior and prognosis.
1 in 7000 live births, 700 dcases each year in the US
What are the parental risk factors of SIDS?
Infant?
Environment?
young maternal age (under 20), maternal smoking, drug abuse in EITHER PARENT.
brain stem abnormalities (medulla), prematurity and or low birth weight, MALES
Environment –> prone, side sleeping, sleeping with parents within first 3 months, sleeping on soft surfaces, hyperthermia
What is the staging for neuroblastoma
stage 1 –> localized tumor with complete excision, no tumor in lymph nodes
2A –> localized tumor with incomplete gross resection
2B –> localized tumor with OR WITHOUT incomplete gross resection… Lymph nodes + with tumor.
3 –> unresectable unilateral tumor
4 –> any tumor with dissemination to distant lymph nodes, bone, bone marrow
4S –> localized tumor with dissemination to skin, liver, and/or bone marrow… limited to infants under 1 year.
how does it work with the first breath taken?
What happens to infants with a deficiency of surfactant?
first breath needs a ton of effort, but it retains 40% of the air and keeps the alveoli open (because of the surfactant) they took in so each breath after that doesn’t need as much work.
lungs collapse with each breath, so infants must work as hard as they did with the first breath as then do with other breaths too!
the most frequent childhood cancers arise in what?
what about in adults?
hematopoietic system, nervous tissue, soft tissues, bone, and kidney
skin, lung, breast, prostate, and colon
Cyclopamine is what?
what’s to note about vitamin A derivative all-trans-retinoic-acid?
plant teratogen –> when pregnant sheep feed on this, the lambs have holoprosencephaly and cylopia
absence of it –> many problems affecting multiple organ systems… but too much of it –> retinoid acid embryopathy –> CNS, cardiac, cleft lip and palate.
What’s the difference between heterotopia from hamartoma?
example of heterotopia?
heterotopia –> microscopically normal cells or tissues that are present in ABNORMAL locations
**pancreatic tissue found in the wall of the stomach
hamartoma –> excessive, focal overgrowth of cells and tissues NATIVE to the organ in which it occurs
Galactosemia:
1) what happens in the kidney?
Galactose-1-phosphate in the kidney impairs aa transport, resulting in aminoaciduria
what are the most common causes of SUIDS?
infections, viral myocarditis, bronchopneumonia
Denys-Drash syndrome
1) what 2 things are they presenting with?
2) what do they have an increased risk of?
3) what risk for Wilms? why is it this high?
Gonadal dysgenesis –> male pseudohermaphroditism
early onset nephropathy –> renal failure
increased risk of GONADOBLASTOMA
90% –> biallelic inactivation of WT1 –> DOMINANT-NEGATIVE MISSENSE MUTATION in the zinc-finger region of the WT1
What is Fetal Hydrops?
what us the generalized edema of the body called?
what is the localized accumulation of fluid called?
accumulation of edema fluid in the fetus during intrauterine growth
hydrops fetalis
cystic hygroma
Most children with wilms tumor present with what?
LARGE abdominal mass that is unilateral or if large enough, extend midline.
Hematuria, pain in the abdomen, intestinal obstruction, hypertension.
what are the 4 benign tumors of childhood?
hemangioma
lymphatic tumor
fibrous tumors
teratomas
Clinical Course and Prognostic features of Neuroblastoma:
1) what do kids usually present with? what age?
2) what do NEONATES present with and what’s the nickname?
3) 90% of these tumors produce what, which makes it an IMPORTANT DIAGNOSTIC FEATURE in BLOOD?.. what do you see increased levels in the URINE?
4) where is a common metastatic site and at what age doe this happen?
`under 2, large abdominal masses, fever, weight loss.
multiple cutaneous metastases that cause deep blue discoloration of the ski –> blueberry muffin baby
catecholamines… although hypertension usually isn’t a problem –> LEADS TO ELEVATED vanillylmandelic acid (VMA) and homovanillic acid (HVA)
periorbital region –> after 2 years old
What maternal abnormalities can attribute to FGR?
what drugs can cause FGR?
what about in developing countries?
maternal conditions that lead to decreased placental blood flow –> preeclampsia, chronic hypertension
teratogens, and some common therapeutic agents like phenytoin.
maternal malnutrition
Deformations:
1) definition
2) how is this similar to disruptions? how is it different?
3) what’s the most common underlying factor?
4) what is an example?
5) what factors can induce this? start with maternal(4), then include placental / fetal (3)
localized or generalized compression of the growing fetus by abnormal biomechanics forces leading to structural abnormalities.
also extrinsic disturbance, but these are more common and not the destruction of an organ or body part
uterine constraint –> 35th and 38th week, rapid increase in the size of the fetus outpaces the growth of the uterus, so the baby undergoes uterine constraint.
clubfeet (from a potter sequence).
first pregnancy, small uterus, malformed uterus, LEIOMYOMAS (he stressed this one).
oligohydramnios, multiple fetuses, abnormal fetal presentation
When you see ganglioneuroma, if there is schwannian stroma, what does this mean?
much more favorable outcome
SIDS vs SUID?
many cases of sudden death in infancy have unexpected anatomic or biochemical basis discernable at autopsy, so this would be Sudden Unexpected Infant Death (SUID)
SIDS we have no idea why despite autopsy
What is immune hydrops?
what hypersensitivity reaction is it?
what causes this?
what are the common antigens known to cause these reactions?
when does it occur? and why?
hemolytic disease caused by blood group antigen incompatibility between mother and fetus
type 2
so the fetus inherits antigenic stuff from the father and that’s considered foreign to the mother, immune response can occur
Rh antigens (D antigen) and ABO blood groups
second and subsequent pregnancies in an Rh-negative mother with an Rh-positive father. –> because at first exposure the mom created IgM antibodies that can’t cross the barrier.
What is considered a major cause of familial predisposition to neuroblastoma?
mutation in anapestic lymphoma kinase (ALK) gene
Neuroblastoma histology:
1) classic neuroblastoma look like what?
2) what is commonly seen in which they are concentrically arranged about a central space filled with fibrillary material?
what do they stain positive for?
small cells with dark nuclei embedded in a faintly eosinophilic NEUROPIL
Homer-Wright Pseudorosettes (or rosettes)
neuron-specific enolase
Histologically, many malignant non-hematopoietic pediatric neoplasms are unique. how?
what does blastoma mean?
they have more primitive (embryonal) undifferentiated appearance –> characterized by sheets of cells with SMALL, ROUND nuclei… they’re called “small round blue cell tumors”
they frequently show features of organogenesis specific to the site of tumor origin…
blastoma –> undifferentiated cells or immature cells
How do we know that a baby might have CF? what do you see on xray?
what’s the specific reasoning why a mutation in the CFTR gene makes it a problem?
meconium ilius –> thick viscid plugs of mucus that are in the small intestine which sometimes cause small-bowel obstruction. –>
microcolon (unused large intestine) –> soap-bubble or frothy pattern, with a dilated small bowel.
it results in defective protein folding in the Golgi and degradation of CFTR before it reaches the cell surface
What is the pathogenesis NRDS?
what’s the fundamental defect?
what genes code for this?
what produces this?
immaturity of the lungs is the MOST important substrate on which RDS develops
pulmonary surfactant.. should be produced at 24, 25, 26 weeks that allow alveoli to stay open with less pressure.
SFTPB or SFTBC genes
type 2 alveolar cells
What is Necrotizing Enterocolitis
1) what do premature children present with?
2) what is it associated with?
3) what ultimately happens?
4) what does it eventually culminate to?
5) what do we see on radiographs?
onset of bloody stools, abdominal distention, and development of circulatory collapse.
Platelet activating factor –> increasing mucosal permeability by promoting enterocyte apoptosis and compromising tight junctions.
ultimately breaking down mucosal barrier –> migration of gut bacteria – inflammation and mucosal necrosis
sepsis and shock
gas within the intestinal wall (pneumatosis intestinalis)he talked about this
What is the L/S ratio?
Lecithin-sphingomyelin ratio for amniotic fluid
if L/S ratio is greater than 2, indicates fetal lung maturity
if less than 2, increased risk of RDS, less than 1.5 is very high risk.
What is the 3 major categories of anomalies and what are the frequencies of each?
why doesn’t this add up to 100%
Genetic causes (12-25%) –> chromosomal (10-15%), Mendelian (2-10%)
Environmental (9-12%)–> Maternal/placental infections (2-3%), Maternal disease states (6-8%), drugs and chems, (1%)
Multifactorial (20-25%) –> MOST COMMON
40-60% of congenital abnormalities are unknown.
Agenesis
Aplasia
Atresia
complete absence of an organ and its associated primordium.
absence of an organ but occurs due to failure of growth of the EXISTING primordium
absence of an opening.. usually a hollow organ like the esophagus
Morphology of Necrotizing enterocolitis:
1) what is usually involved?
2) 20-60% of patients need what?
3) those who get over the problem end up having what?
4) what do you see under the microscope?
terminal ileum, cecum, right colon (usually)
resection of the necrotic segments of the bowel.
post-necrotizing enterocolitis strictures from fibrosis
gas bubbles, ulceration, colonization, coagulative necrosis
what are the most common neoplasms of childhood and how does this differ from kids?
Soft-tissue tumors of mesenchymal
most common in adults are epithelial origin.
What infections are most common for FGR infants?
TORCH (toxoplasmosis, Rubella, Cytomegalovirus, herpesvirus)
